title: An intestinal factor intelectin-1 maintains anti-asthmatic environment via gut-bone-lung axis

city: Changsha

first: Shiyue

last: He

state: other

address: Changsha, China

institute: Xiangya Hospital, Central South University

summary: The development of extra-intestinal diseases is often accompanied by disruptions in intestinal microbiota and their metabolites. Improvement of the intestinal microenvironment frequently results in amelioration of these diseases, highlighting the need to identify key regulatory intestinal factors. In our asthma study, we identified intelectin-1 (ITLN1), predominantly expressed in the intestine, as a critical factor in maintaining intestinal bacterial homeostasis to mitigate allergic asthma via gut-bone-lung axis. We observed that reduced serum ITLN1 levels in asthmatic patients were significantly associated with increased disease severity and airway inflammation. In house dust mite (HDM)-induced asthma mouse model, ITLN1 deficiency exacerbated allergic inflammation by disrupting gut microbial homeostasis, resulting in decreased production of the beneficial short-chain fatty acid butyrate due to reduced Erysipelotrichaceae, Muribaculaceae, and Bifidobacteriaceae levels. Butyrate reduction increased CCL8 secretion by lung macrophages, which facilitated the recruitment of CD4+ T cells from the bone marrow to the lungs through the CCL8-CCR3 axis and enhanced group 2 innate lymphoid cells immune response, thereby amplifying type 2 inflammation. Elevated CCL8 levels were detected in both asthmatic patients and ITLN1-deficient asthmatic mice. Notably, supplementation with either ITLN1 or butyrate, as well as neutralization of CCL8, effectively attenuated lung allergic inflammation and improved asthma outcomes. Our findings establish ITLN1 as a crucial mediator that links gut microbial metabolism to pulmonary immune regulation, providing insights into the gut-bone-lung axis as a regulatory mechanism in asthma pathogenesis. These results position ITLN1 as a promising therapeutic target for modulating the intestinal microenvironment and mitigating systemic inflammatory responses in asthma and related disorders.

overall_design:
To explore the genes that plays key roles in the asthma model with Itln1 deiffcient mice compared to asthma model with wild type mice,  we processing RNA sequencing in lung tissues between these two types.
We then performed gene expressing profiling analysis using data from RNA-seq of the above two models of lung tissue.

first: Xinyue

last: Hu


title: DNA methylation and transcriptome integration analysis reveals potential markers associated with the pathogenesis of type A aortic dissection [miRNA-seq]

status: Public on Dec 09 2025

city: Tianjin

first: chao

last: chang

address: South Taierzhuang Road

country: China

institute: Tianjin University,Tianjin Chest Hospital

type: Non-coding RNA profiling by high throughput sequencing

summary: This study aimed to identify candidate markers of TAAD by integrating methylation and transcriptome sequencing analyses.

overall_design: Aortic vascular tissue samples from TAAD cases and controls were used for transcriptome sequencing and methylation analysis using the Illumina Hiseq sequencing platform and Illumina Infinium MethylationEPIC BeadChip microarray, respectively. A series of bioinformatics analyses and machine learning algorithms were used to identify key methylated genes from the differentially expressed genes and differentially methylated sites between TAAD and controls.

first: Chao

last: Chang

first: Qingliang

last: Chen


title: Knockout of MARCO block TLR3-IL-1β dependent inflammatory response in chicken macrophages

city: Yangzhou

first: Xuming

state: Jiangsu

address: No.48 East Wenhui Road

department: College of Animal Science and Technology

institute: Yangzhou University

type: Expression profiling by high throughput sequencing

summary: The scavenger receptor MARCO mediate double-stranded RNA (dsRNA) uptake through binding to viral dsRNA at the cell surface and to enable this dsRNA to interact with the important dsRNA recognition receptor TLR3 in the endosome. To investigate the antiviral function of MARCO in ALV-J infection, we knocked out the MARCO gene in HD11 cells using the CRISPR/Cas9 technique and then performed RNA-sequencing on wild-type and mutant macrophages. Under the presence of MARCO, macrophages response to viral infection through inducing TLR3-IL-1β dependent inflammatory response. Conversely, lack of MARCO increased the viral replication levels and attenuated the antiviral inflammatory response.

first: Xujing

first: Huixian

last: Wu

first: Hengmi

last: Cui


title: DNA methylation and transcriptome integration analysis reveals potential markers associated with the pathogenesis of type A aortic dissection

type: Methylation profiling by genome tiling array

overall_design: Aortic vascular tissue samples from TAAD cases and controls were used for transcriptome sequencing (GSE267434) and methylation analysis using the Illumina Hiseq sequencing platform and Illumina Infinium MethylationEPIC BeadChip microarray, respectively. A series of bioinformatics analyses and machine learning algorithms were used to identify key methylated genes from the differentially expressed genes and differentially methylated sites between TAAD and controls.


title: Gene expression data of PBMC and hippocampus of young rats with metabolically obese, normal-weight phenotype and normal-weight controls

city: Palma

first: Paula

last: Oliver

address: Cra. Valldemossa km 7.5

country: Spain

institute: University of the Balearic Islands

summary: The metabolically obese, normal-weight (MONW) phenotype is characterized by visceral adiposity and obesity-related complications like insulin resistance or even cognitive impariment, despite a lack of excess body weight. Thus, early identification of individuals with this phenotype is crucial for implementing effective preventive strategies. Peripheral blood mononuclear cells (PBMC) serve as valuable source of biomarkers in obesity research since they can be collected with minimun invasiveness and are able to reflect gene expression alterations in internal organs, such as the liver or brain. This study aims to analyze alterations in gene expression profile in PBMC and the hippocampus of young rats with MONW phenotype induced by the intake of a high-fat diet, compared to normal-weight controls. Altered transcriptomic profiles in these biological samples can help to identify early biomarkers of metabolic damage related to the MONW phenotype. Furthermore, we aim to investigate the potential therapeutic effects of perinatal treatment with the anti-obesity hormone leptin on metabolic health in MONW animals.

overall_design: Two-month-old virgin female Wistar rats were mated with male rats. After matching, females were placed in individual cages with free access to water and food. On day 1 after delivery, excess pups in each litter were removed to keep 10 pups per dam. Male pups from a total of 8 litters were randomly assigned into 2 groups receiving different experimental treatments from day 1 to day 20 of lactation during the first 2 h of the beginning of the light cycle: Control (n = 16), leptin (n = 10). All treatments were administered orally. A solution of recombinant murine leptin (PeproTech, London, UK) dissolved in Captisol® was administered to leptin group. The amount of leptin administered to the animals was calculated as five times the average amount of daily leptin intake from breast milk; the Control group received the same volume of the vehicle, Captisol®. On day 21, after weaning, male rats were single-caged and kept on a normolipidic control balanced diet (D12450B, Research Diets). On day 23, the Control group rats were randomly assigned to two groups: normal-weight, CTRL group (n = 8), fed ad libitum a standard chow diet with 10% calories from fat (D12450B, Research Diets); and MONW, HF group (n = 8), fed a chow diet with 60% calories from fat (D12492, Research Diets), administered under isocaloric conditions to CTRL, to prevent development of obesity. Moreover, the leptin treated group, LEP group (n=10) received the same hyperlipidic diet as the HF group, also administered under isocaloric conditions relative to the CTRL group.  Animals were maintained on these diets for 11 weeks. At the age of 3.5 months, blood samples (1.5-2 ml) were collected in feeding conditions from the saphenous vein using EDTA 100 mM as an anticoagulant. PBMC fraction was isolated by Optiprep™ (Sigma Aldrich Química SA, Madrid, Spain) density gradient separation according to the manufacturer’s instructions, and stored at -80ºC until RNA extraction. At 14 weeks of age, i.e., 3.5 months, animals were sacrificed by decapitation under ad libitum feeding conditions. The hippocampus was rapidly removed, frozen in liquid nitrogen, and stored at -80ºC until RNA extraction. Global gene expression was explored in PBMC and hippocampus by microarray analysis.

first: Carmen

last: García-Ruano

first: Andrea

last: Costa

first: Andreu

last: Palou


title: High-intensity pulse magnetic field promotes Escherichia coli division by affecting glucose metabolism

city: Wuhan

first: Pengbo

last: Wang

state: Hubei

address: hongshan street

institute: Huazhong university of science and technology

summary: The biological effects of magnetic field (MF) have been studied and applied in medicine over the past four decades. However, high-intensity pulse magnetic field (HI-PMF), which may exert stronger biological effects in a shorter time, is rarely studied. Herein, this study aims to investigate the biological effects of 2.5 T HI-PMF on Escherichia coli and the consequent physiological alterations. After being treated by HI-PMF, a notable increase in intracellular NADH/NAD+ ratio was observed, accompanied by an enhanced survival rate. Transcriptome analysis revealed significant changes in genes associated with glycolysis, TCA cycle and oxidative phosphorylation, suggesting that HI-PMF induces an increase in glucose metabolism. Interestingly, the decreased intracellular glucose concentration could alleviate the inhibition of cell division, which was identified as the reason for the increased survival rate after being treated by HI-PMF. Conversely, low intracellular glucose level led to cell death under HI-PMF. Therefore, the results suggest that HI-PMF treatment promotes cellular glucose metabolism and further influences cell survival depending on intracellular glucose concentrations.

overall_design: To invesitage the influence of 2.5 T HI-PMF on E. coli, we transformed a endogenous fluorescence probe SoNar to E. coli and observed its changes. Then we performed gene expression profiling analysis using data from RNA-seq from cells with or without HI-PMF treatment.


title: Knockdown of chERVs block TLR3-IL-1β dependent inflammatory response in chicken macrophages

summary: Chicken endogenous retroviruses (chERVs) are remnants of ancient retroviral infections and can profoundly affect the host antiviral innate immune response, although the mechanisms by which these changes occur are largely unknown. To investigate the antiviral function of chERVs in ALV-J infection, we knocked down the expression of chERVs in HD11 cells using the CRISPR/Cas9 technique and then performed RNA-sequencing on wild-type and mutant macrophages. Under the presence of chERVs, macrophages response to viral infection through MARCO-TLR3-IL-1β dependent inflammatory response. Conversely, knowndown of chERVs increased the viral replication levels and attenuated the antiviral inflammatory response.


title: Ketogenic regulation of histone modification by CDK4 promotes leukemogenesis [RNA-seq]

first: Jin

last: Xu

address: 115 East Lake Road, Wuhan, Hubei, 430071, P. R. China

institute: Wuhan university

summary: While ketogenic nutrition shows promise as an adjunct to conventional cancer therapies, its efficacy varies depending on the type of cancer and its specific metabolic characteristics. How ketone bodies affect tumorigenesis and how the ketogenic pathway becomes deregulated in cancer remain to be fully understood. Using T-cell acute lymphoblastic leukemia (T-ALL) as a model, we here demonstrate that ketogenic metabolite β-hydroxybutyrate (BHB) plays a remarkable pro-leukemogenic role in mice. T-ALL cells generally exhibited greater expression of β-hydroxybutyrate dehydrogenase (BDH1), the metabolic enzyme that leads to cell autonomous synthesis of BHB. Mechanistically, aberrant CDK4 activation enables direct phosphorylation of BDH1 at the serine 296 residue and enhances its protein stability. Importantly, BDH1 deficiency leads to robust growth inhibition and cell death of human T-ALL cells, and markedly impedes NOTCH1-induced T-ALL progression in mice. BDH1-mediated production of BHB enhances the histone modification of β-hydroxybutyrylation (Kbhb), thereby leading to transcriptional activation of pro-leukemogenic genes MYC and NKX3.1. These findings shed light on how oncogenic CDK4 deregulates ketogenesis and promotes leukemia progression via an epigenetic mechanism. Therefore, ketogenic diets or ketone supplements should be taken with caution by cancer patients. Therapeutic interventions targeting key ketogenic enzymes may hold great promise for leukemia treatment.

overall_design: To confirm the pivotal role of MYC and NKX3.1 as a significant downstream target of BDH1, we performed the transcriptome analysis in BDH1-depleted Jurkat cells while MYC was restored.

first: Guoliang

last: Qing

first: Hudan

last: Liu


title: Comprehensive search for Target genes of miR-199a-3p, miR-99b-3p and miR-140-5p in neural cells.

city: Tokorozawa

first: Yusuke

last: Mizohata

address: Namiki 3-2

country: Japan

institute: National Defense Medical College

summary: the expression of 167, 86, and 44 mRNAs was found to be significantly downregulated in Neuro-2A cells, primary astrocytes and BV-2 cells, respectively.

overall_design: Equal amounts of three custom miRNA mimics (miR-199a-3p, miR-99b-3p and miR-140-5p) (Horizon) (Supplementary Table 16) and Dharmafect 1 (T-2001, Horizon) were mixed to form a complex using PS-free serum-free medium. The mimic-Dharmafect1 complex was then diluted with complete medium to 25 nM. For the control mimic, cel-miR-67 was used (Horizon). After cultivation in PS-free medium (37°C, 5% CO2, 24 h), the cells were incubated in a transfection medium for 24 h. Following transfection, RNA was extracted using QIAzol lysis reagent. Finally, the obtained RNA samples were analysed by NGS (DNA Chip Research Institute, Tokyo, Japan). Cell seeding was conducted at 6.0×105 cells/mL for Neuro-2A cells, at 9.0×105 cells/mL for primary astrocytes and at 3.0×105 cells/mL for BV-2 cells.

last: Yoshioka

first: Takahiro

last: Ochiya

first: Yuji

last: Morimoto


title: Proteogenomic discovery of novel open reading frames with HLA immune presentation on human beta cells

city: Aurora

first: Neelanjan

last: Mukherjee

state: Colorado

address: Research Complex 1 South, 12801 E 17th Ave

department: Biochemistry and Molecular Genetics

country: USA

institute: University of Colorado School of Medicine

summary: Ribosome profiling (Ribo-seq) provides a comprehensive view of translational regulation, crucial for understanding cellular processes. Here, we applied Ribo-seq to map the translatome of human stem cell-derived beta cells (sBCs). Our analysis revealed close to 1000 novel open reading frames (nuORFs) in sBCs, with a majority showing protein-level support, suggesting functional relevance. Furthermore, we detected an immunogenic peptide, INS-DRiP, originating from an alternative start site in INS mRNA. Comparison with primary human islets highlighted beta cell specificity of the identified nuORFs. Notably, we identified a regulatory upstream ORF within TYK2, a gene implicated in type 1 diabetes (T1D) and crucial for beta cell function and interferon response. Our findings underscore the importance translational regulation in beta cell function and its implications in T1D.

overall_design: FLAG-RPL22 IP ribosome profiling samples from hPSC cells, DE cells and stem cell derived beta-cells all differentiated from hPSC cells and RNA-seq samples from INS promoter driven GFP sorted stem cell derived beta cells.

first: Kathryn

last: Walters

first: Roberto

last: Castro-Gutierrez

first: Amber

last: Baldwin

first: Holger

last: Russ


title: Gene expression profiles at single cell level of TSLP producing cells in mouse intestinal lamina propria.

city: San Francisco

first: Richard

last: Locksley

state: CA

address: 513 Parnassus Avenue

institute: University of California, San Francisco

summary: We used TSLP reporter mouse line to identify the cell sources of TSLP in the intestine.

overall_design: TSLP-tdTomato positive cells in the intestinal lamia propria were isolated using fluorescence-activated cell (FACS) sorting and analyzed using scRNA-seq.

first: Liao

last: Chang

first: Ji

last: Ming

first: Wang

last: Zhien

first: Drucker

last: Daniel Joshua

first: Liang

last: Hong-Erh

first: Locksley

last: Richard Michael


title: Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas

city: Boston

first: Carlos Alberto

middle: Oliveira de

last: Biagi Junior

state: MA

address: 360 Longwood Ave

department: Pediatric Oncology

institute: Dana Farber Cancer Institute

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

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

overall_design: Refer to individual Series


title: Escape from X inactivation is directly modulated by Xist non-coding RNA [cell line RNA-seq]

city: Solna

first: Jasper

last: Panten

address: Tomtebodavägen 23

country: Sweden

institute: SciLifeLab

summary: X-chromosome inactivation silences one copy of the X-chromosome in female cells, but a number of genes escapes this inactivation. We asked whether increased levels of Xist RNA, the molecular actor driving X-inactivation, impacts expression levels of escapees. To this end, we performed transcriptomic profiling of X-linked gene expression in clonal neural progenitor cell lines with transgenes that allow for the overexpression of Xist on the inactive X chromosome. We perform Xist overexpression experiments for up to three weeks and also test the reversibility of Xist overexpression using washout experiments. Finally, we demonstrate the role of SPEN in Xist-mediated silencing of escape using an inducible degron.

sample_organism:
Mus
Mus musculus

platform_organism:
Mus
Mus musculus

overall_design: Clonal neural progenitor cell lines were generated by differentiating first generation hybrid embryonic stem cells (from a C57BL6/J x CAST/EiJ cross). All cell lines carry an inactive B6 X chromosome and a doxycycline-inducible transgene on the Xi. Doxycyclin treatment for 3, 7, 14 and 21 days was performed in the E6 cell line and allele-specific expression was measured using RNA-Sequencing. Furthermore, multiple timepoints after washing out doxycycline were analyzed to assess reversibility. To test the effect of SPEN in Xist-induced silencing, the CL30/CL31 cell lines were used in which SPEN is fused to an auxin-inducible degradation domain. Combined treatment with auxin and doxycycline was used to assess silencing in the absence of SPEN.

first: Edith

last: Heard

first: Agnese

last: Loda

first: Antonia

last: Hauth


title: Escape from X inactivation is directly modulated by Xist non-coding RNA [methylation]

type: Methylation profiling by high throughput sequencing

summary: X-chromosome inactivation silences one copy of the X-chromosome in female cells, but a number of genes escapes this inactivation. We asked whether increased levels of Xist RNA, the molecular actor driving X-inactivation, impacts expression levels of escapees. To this end, we performed DNA methylation profiling of X-linked genes in clonal neural progenitor cell lines with transgenes that allow for the overexpression of Xist on the inactive X chromosome. We perform Xist overexpression experiments for up to three weeks and also test the reversibility of Xist overexpression using washout experiments.

overall_design: Clonal neural progenitor cell lines were generated by differentiating first generation hybrid embryonic stem cells (from a C57BL6/J x CAST/EiJ cross). All cell lines carry an inactive B6 X chromosome and a doxycycline-inducible transgene on the Xi. Doxycyclin treatment for 7 and 21 days was performed in the E6 cell line and allele-specific DNA methylation was measured. Furthermore, washing out doxycycline was analyzed to assess reversibility.


title: Escape from X inactivation is directly modulated by Xist non-coding RNA [ATAC-seq]

type: Genome binding/occupancy profiling by high throughput sequencing

summary: X-chromosome inactivation silences one copy of the X-chromosome in female cells, but a number of genes escapes this inactivation. We asked whether increased levels of Xist RNA, the molecular actor driving X-inactivation, impacts epigenetic marks around escapees. To this end, we performed chromatin accessibility profiling of X-linked genes in clonal neural progenitor cell lines to identify cis-regulatory elements active in these cell lines.

overall_design: Clonal neural progenitor cell lines were generated by differentiating first generation hybrid embryonic stem cells (from a C57BL6/J x CAST/EiJ cross). All cell lines carry an inactive B6 X chromosome. Chromatin accessibility was measured in two replicates using ATAC-Seq.


title: Escape from X inactivation is directly modulated by Xist non-coding RNA [in vivo]

summary: X-chromosome inactivation silences one copy of the X-chromosome in female cells, but a number of genes escapes XCI. We asked whether increased levels of Xist RNA, the molecular actor driving X-inactivation, impacts expression levels of escapees. We tested whether dox-mediated Xist-overexpression affected the expression levels of escapees during mouse early embryonic development.

overall_design: To investigate the effect of Xist overexpression on escape levels in early embryos, Xist was overexpressed via doxycycline induction in early mouse embryos carrying an inducible Xist allele on the inactive X. Embryos were derived from natural mating between C57BL/6 TX males Xptet/Y; R26rtTA/WT with wild type JF1 females. Embryos were harvested at E2.5 and E3.5 and cultured in vitro in the presence of Doxycycline for 24 hours. Embryos were harvested for RNA-Sequencing using the Smart-Seq2 protocol and allele-specific expression was determined for X-linked genes.

first: Emma

last: Kneuss


title: Bulk RNA-seq data of orbital fibroblasts and peripheral blood mononuclear cells (PBMCs) from thyroid eye disease patients

city: Shanghai

first: Jin

last: Liu

state: Huangpu district

address: 833 Zhizaoju Road

institute: Shanghai Ninth People’s Hospital

summary: Smoking affects the severity of TED manifestations as well as patients’ responses to medication. However, the underlying pathogenic mechanisms of smoking remain largely unclear in TED.To address these issues, we conducted bulk RNA-seq to distinguish orbital fibroblats under different time of treatment of cigarette smoking extract (CSE) from control. Besides, bulk RNA-seq was performed to unravel transcriptional differences between TED patients with or without smoking habits.

overall_design: For orbital fibroblast cell sequencing, orbital fibroblast cells were treated with CSE for different time ranging from 6h to 72h (group names as T6h, T8h, T12h, T24h, T48h, T72h), while control group was cultured in Dulbecco’s Modified Eagle Medium (group name as Control). For TED patients' PBMCs sequencing, PBMCs from 19 patients with smoking habit (smoking patient) and 19 patients without smoking habit (nonsmoking patient) were analyzed.

first: Tianyi

last: Zhu

first: Sijie

last: Fang

first: Huifang

last: Zhou


title: ACSS2 upregulation enhances neuronal resilience to aging and neurodegeneration [RNA-seq]

city: Philadelphia

first: Shuo

last: Zhang

state: PA

address: 3400 Civic Center Blvd

institute: University of Pennsylvania

summary: Epigenetic mechanisms, including histone acetylation, play a key role in learning and memory, with recent evidence of a role in neuronal function in Alzheimer?s disease and Related Dementia (ADRD). Acetyl-CoA synthetase 2 (ACSS2), an enzyme that generates acetyl-CoA, is central to histone acetylation and gene regulation, particularly in neurons, due to their unique metabolic demands and their postmitotic state. ACSS2 can be recruited to the nucleus and to chromatin, locally supplying acetyl-CoA to directly fuel histone acetyltransferase enzymes and key neuronal gene expression. This regulatory mechanism may be a promising target for therapeutic intervention in neurodegenerative diseases because systemic ACSS2 deletion in mice, although largely normal in physiology, is greatly impaired in memory. Here we investigated whether increasing levels of ACSS2 could protect neurons against disease and age-associated cognitive decline. Given the role of tau in ADRD, we used primary hippocampal neurons that mimic the sporadic development of tau pathology, and used the P301S transgenic mouse model for tau-induced memory decline. Our results show in these in vitro and in vivo models of tauopathy, that ACSS2 upregulation mitigates tau-induced transcriptional alterations, enhances neuronal resilience against tau pathology, improves long-term potentiation, and ameliorates memory deficits. Expanding upon these findings, we investigated deficits in aged mice, and reveal that increasing histone acetylation through ACSS2 upregulation improves age-associated memory decline. These findings indicate that increasing ACSS2 is highly effective in countering age- and tau-induced transcriptome changes, preserving elevated levels of synaptic genes, and safeguarding synaptic integrity. We thus highlight ACSS2 as a key player in the epigenetic regulation of cognitive aging and ADRD, providing a foundation for targeted therapeutics to enhance brain resilience and function.

overall_design: To investigate the transcriptomic changes induced by ACSS2 upregulation in mouse primary hippocampal neurons

first: Naemeh

last: Pourshafie

first: Shelley

middle: L

last: Berger

first: Nancy

middle: M

last: Bonini

first: Desi

middle: C

last: Alexander


title: Escape from X inactivation is directly modulated by Xist non-coding RNA [multiclone]

summary: X-chromosome inactivation silences one copy of the X-chromosome in female cells, but a number of genes escapes this inactivation. We asked whether increased levels of Xist RNA, the molecular actor driving X-inactivation, impacts expression levels of escapees. To this end, we performed transcriptomic profiling of X-linked gene expression in clonal neural progenitor cell lines with varying Xist levels.

overall_design: Clonal neural progenitor cell lines were generated by differentiating first generation hybrid embryonic stem cells (from a 129/Sv x CAST/EiJ cross). Clones from 21 cell lines were generated in three independent experiments. RNA-Sequencing was performed for each cell line. Using heterozygous variants between the two strains, allele-specific expression of X-linked genes was quantified together with Xist expression.


title: ACSS2 upregulation enhances neuronal resilience to aging and neurodegeneration [Cut&Run]

summary: Epigenetic mechanisms, including histone acetylation, play a key role in learning and memory, with recent evidence of a role in neuronal function in Alzheimer’s disease and Related Dementia (ADRD). Acetyl-CoA synthetase 2 (ACSS2), an enzyme that generates acetyl-CoA, is central to histone acetylation and gene regulation, particularly in neurons, due to their unique metabolic demands and their postmitotic state. ACSS2 can be recruited to the nucleus and to chromatin, locally supplying acetyl-CoA to directly fuel histone acetyltransferase enzymes and key neuronal gene expression. This regulatory mechanism may be a promising target for therapeutic intervention in neurodegenerative diseases because systemic ACSS2 deletion in mice, although largely normal in physiology, is greatly impaired in memory. Here we investigated whether increasing levels of ACSS2 could protect neurons against disease and age-associated cognitive decline. Given the role of tau in ADRD, we used primary hippocampal neurons that mimic the sporadic development of tau pathology, and used the P301S transgenic mouse model for tau-induced memory decline. Our results show in these in vitro and in vivo models of tauopathy, that ACSS2 upregulation mitigates tau-induced transcriptional alterations, enhances neuronal resilience against tau pathology, improves long-term potentiation, and ameliorates memory deficits. Expanding upon these findings, we investigated deficits in aged mice, and reveal that increasing histone acetylation through ACSS2 upregulation improves age-associated memory decline. These findings indicate that increasing ACSS2 is highly effective in countering age- and tau-induced transcriptome changes, preserving elevated levels of synaptic genes, and safeguarding synaptic integrity.  We thus highlight ACSS2 as a key player in the epigenetic regulation of cognitive aging and ADRD, providing a foundation for targeted therapeutics to enhance brain resilience and function.

overall_design: Cut&Run-seq for mouse primary hippocampal neurons treated with hAD-tau or PBS.


title: A Nuclear Isoform of Hydroxyacyl-CoA Dehydrogenase Inhibits Tumor Progression In Colorectal Cancer

city: hangzhou

first: Yunyi

last: Gao

state: Zhejiang

address: Zijingang Campus of Zhejiang University,Yuhangtang Road No.388

institute: Zhejiang university

summary: Alternate translation initiation expands protein diversity which is adopted by cancers for progression. However, the majority of these alternative initiation events in cancers remain largely undefined. In this study, we demonstrate that the human hydroxyacyl-CoA dehydrogenase (HADH) gene, catalyzing the third step of the mitochondrial β-oxidation cascade, has two alternative translation start codons. The translation from the downstream start codon produces a short isoform (HADH-S) primarily localized in the nucleus. HADH-S is downregulated in colorectal cancer. Overexpression of HADH-S inhibits colorectal tumorigenesis in vitro and in vivo. Mechanistically, HADH-S antagonizes protein arginine methyltransferase 5 (PRMT5)-mediated histone arginine methylation, thereby facilitating gene transcription. Notably, HADH promotes the transcription of the Wnt suppressor AXIN2. These findings collectively identify a novel nuclear isoform of HADH that exerts inhibitory effects on colorectal tumorigenesis.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for HADH-S in RKO cells. To explore the target genes of HADH-S in CRC cells, we conducted RNA-seq in both control RKO cells and RKO cells overexpressing HADH-S.

first: Lei

last: Yu

first: Xiangwei


title: Cardiac Fibrosis in Dilated Cardiomyopathy: Transcriptomics Insights, Histological Correlations, and Organoid Model Verifications [RNA-seq II]

city: Kyoto

first: Yoshinori

last: Yoshida

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

institute: Kyoto University

summary: Dilated cardiomyopathy (DCM) represents a leading cause of heart failure among younger adults. Despite endomyocardial biopsy (EMB) transcriptome enriching our understanding of DCM, the link between its gene expression and phenotype remains unclear. RNA-seq analysis of 58 DCM samples and 12 publicly available control samples unveiled about 25,000 transcripts. A principal component analysis highlighted a distinct DCM-control separation. WGCNA revealed four transcriptome modules strongly associated with DCM. The purple module, which is the DCM-related module, was enriched with fibrosis-related genes and showed FSTL3 as a pivotal DCM-associated gene. , We further validated using cardiac fibrosis organoid models. Concurrently, FSTL3 expression reflected cardiac organoid fibrosis intensity. Furthermore, FGFR1 expression, along with its phosphorylation in DCM myocardial tissue, was correlated with fibrosis severity. Cardiac fibrosis organoid models treated with AZD4547, a selective FGFR1 inhibitor, suppressed fibrosis-related markers, underscoring its potential therapeutic efficacy against DCM-related cardiac fibrosis.

overall_design: We established a cardiac organoid model using human induced pluripotent stem cell (hiPSC)-derived ventricular cardiomyocytes and epicardial cells. Three groups were compared: Control (n=3), Fibrotic condition (n=3), and Fibrotic condition treated with AZD4547 (n=3).

first: Reo

last: Hata


title: Cardiac Fibrosis in Dilated Cardiomyopathy: Transcriptomics Insights, Histological Correlations, and Organoid Model Verifications


title: Gene expression profile at single cell level of neural cells from the cervical embryonic chick neural tube at 66 hours of development (HH18)

city: PARIS

first: Stephane

last: Le Crom

address: 46 rue Ulm

department: Genomic Core Facility

country: France

institute: IBENS

summary: Neural progenitors are considered as an homogenous population in the neural epithelium. We used single cell RNA sequencing (sc-RNA-seq) to analyze their diversity in the neural tube

overall_design: Cervical part of neural tubes (spanning 5 somites starting from somite n°8) were dissected at HH18 and dissociated and analyzed using scRNAseq.

first: Fanny

last: Coulpier

first: Nathalie

last: Lehman

first: Morgane

middle: T

last: Chollier

first: Rosette

last: Gaïame

first: Evelyne

last: Fischer

first: Xavier

last: Morin

first: Baptiste

last: Mida


title: Pomalidomide as an immune-enhancing agent in samples from people living with HIV

city: Melbourne

first: Rachel

last: Pascoe

state: VIC

address: 792 Elizabeth Street

department: Microbiology and Immunology

country: Australia

institute: University of Melbourne

summary: Persisting immune dysfunction in people living with HIV (PLHIV) on suppressive antiretroviral therapy (ART) is a key challenge to finding a cure for HIV. We investigated pomalidomide, a well-tolerated immunomodulatory drug, as an agent to enhance HIV-directed immune responses. We collected peripheral blood mononuclear cells (PBMC) from PLHIV on ART, cultured these in the presence of HIV peptides and found that pomalidomide significantly expanded tetramer-positive HIV-specific CD8+ T-cells with reduced markers of exhaustion and enhanced CD8+ T-cell-mediated killing of HIV-target cells. This was associated with an upregulation of carbon metabolism and cell cycle pathways, with MYB and BATF3 implicated as key regulators of the pomalidomide-mediated response. Pomalidomide also enhanced NK cell cytotoxicity against K562 as well as HIV-infected target cells by expanding polyfunctional cytotoxic NK cells. Given its immune-enhancing potential and good safety profile, pomalidomide should be further investigated as a therapeutic strategy for HIV control and cure.

overall_design: PBMC from six people living with HIV on suppressive ART were exposed to HIV antigen and treated with either DMSO or pomalidomide (0.25 uM) for 13 days. MHC-I:HIV peptide tetramers were used to isolate HIV-specific CD8+ T cells, and cells were sequenced using Illumina TruSeq.

middle: D

first: Jan

last: Schröder

first: Stephen

last: Wilcox

first: Sharon

middle: R

last: Lewin

first: Thomas

middle: A

last: Rasmussen


title: Molecular and phenotypic blueprint of human hematopoiesis links proliferation stress to stem cell aging

city: Milan

first: Raffaella

last: Di Micco

address: Via Olgettina, 60

country: Italy

institute: San Raffaele Telethon Institute for Gene Therapy

summary: Hematopoietic stem/progenitor cell (HSPC) aging has been associated with myeloid skewing, reduced clonal output, and impaired regenerative capacity, but quantitative immunophenotypic and functional analysis across human aging is lacking. Here, we provide a comprehensive phenotypic, transcriptional, and functional dissection of human hematopoiesis across the lifespan. Although primitive hematopoietic stem cell (HSC) numbers were stable during aging, overall cellularity was reduced, especially for erythroid and lymphoid lineages. Notably, HSPC from aged individuals had similar repopulating frequency of younger counterparts in primary and secondary xenografts; yet aged HSC displayed impaired differentiation capacity, changes in chromatin accessibility, dysregulation of cell cycle, and a reduced capacity to counteract activation-induced proliferative stress with concomitant accumulation of DNA damage and senescence-like features upon xenotransplantation. This age-associated phenotypic and functional decline was recapitulated by enforcing proliferative stress in vivo on human HSPC. Overall, our work sheds light on dysregulated responses to activation-induced proliferation underlying HSPC aging and establishes xenotransplantation-based models as suitable for studying age-associated hematopoietic defects.

overall_design: RNA-seq analysis of primary HSPCs from bone marrow, cell culture over night

first: Emanuele

last: Lettera

first: Serena

last: Scala

first: Giacomo

last: Farina


title: Adapters drive context-dependent Mycobacterial ClpX activity by altering conformational sampling

city: Delhi

first: Vinay

middle: K.

last: Nadnicoori

state: DELHI

address: National Institute of Immunology, Near JNU EAST GATE, ARUNA ASAF ALI MARG, NEW DELHI-110067

country: India

institute: National Institute of Immunology

summary: The AAA+ ATPase ClpX recognizes diverse substrates and plays a crucial role in cellular homeostasis. Mycobacterium tuberculosis (Mtb) ClpX binds to two structurally distinct adaptors- the Single-stranded DNA binding protein (SSB) and the Small protein B (SmpB).  The mechanistic features of adaptor-dependent modulation of ClpX activity and its functional implications still remain poorly understood.  Results show that both adaptors bind to the N-terminal domain of ClpX, albeit with different stoichiometry. While SSB binding enhances ATPase activity, SmpB does not.  Structural and biochemical experiments revealed that both adaptors substantially reduce conformational sampling and drive ClpX into a more compact, homogenous quaternary arrangement.  The interactome of the adaptors and ClpX indicate features that distinguish adaptor-dependent from adaptor-independent ClpX activity.  Changes in the expression profile in Mtb cells upon over-expression of either SSB or SmpB suggest functional linkages between the protein recycling mechanism and transcription.  Mtb ClpX is thus both- an unfoldase driving protein maturation and a checkpoint regulator synchronizing transcription and translational processes in this slow-growing human pathogen.

overall_design: To investigate the downstream role of SSB and SmpB, the transcriptomics of the vector control Rv strain (Rv::pN), and overexpressing strains of ssb (Rv::pN-ssb) and smpB (Rv::pN-smpB) was performed

first: Ashish

last: Deshmukh

first: Sidra

last: Khan

last: Nandicoori

first: Balasubramanian

last: Gopal


title: Rice Chromatin Protein OsHMGB1 Is a Transcriptional Facilitator that Regulates Phosphate Homeostasis and Plant Growth [RNA-seq II]

city: Hangzhou

first: Yan

last: Wang

address: 866 Yuhangtang Road, Xihu District, Hangzhou City, Zhejiang Province, China

department: College of Life Sciences

institute: Zhejiang University

summary: Although phosphorus is one of the most important essential elements for plant growth and development, the epigenetic regulation of inorganic phosphate (Pi) signaling is poorly understood. In this study, we identified the high-mobility-group protein OsHMGB1 as a key regulator of phosphate homeostasis and plant growth in rice (Oryza sativa). OsHMGB1 expression is induced by Pi starvation and encodes a nucleus-localized protein. Relative to wild-type plants, Oshmgb1 mutant plants had lower Pi content in their leaves, whereas plants overexpressing OsHMGB1 had higher Pi content, indicating that OsHMGB1 positively regulates Pi accumulation. Transcriptome deep sequencing and chromatin immunoprecipitation followed by sequencing showed that OsHMGB1 regulated the expression of a series of phosphate starvation responsive (PSR) genes by binding to their promoters. Furthermore, Assay for Transposase-Accessible Chromatin followed by sequencing revealed that OsHMGB1 was involved in maintaining chromatin accessibility. Indeed, OsHMGB1 occupancy positively correlated with genome-wide chromatin accessibility and gene expression levels. Notably, we determined that OsHMGB1 interacted with RNA polymerase II to help regulate transcription, especially under low Pi conditions. Taken together, our results suggest that OsHMGB1 functions as a transcriptional facilitator, revealing a key epigenetic mechanism to regulate Pi homeostasis and fine-tune plant acclimation responses to Pi-limited environments.

overall_design: Correlation analysis of RNA-seq data (gene expression profile) and ATAC-seq data (genome-wide accessibility)  for Oshmgb1 mutans and wild-type (WT) plants under HP conditions.

first: Fei

first: Hong

last: Lu

first: Rongbin

last: Lin


title: Cardiac Fibrosis in Dilated Cardiomyopathy: Transcriptomics Insights, Histological Correlations, and Organoid Model Verifications [RNA-seq I]

first: Yoshinori

last: Yoshida

summary: Dilated cardiomyopathy (DCM) represents a leading cause of heart failure among younger adults. Despite endomyocardial biopsy (EMB) transcriptome enriching our understanding of DCM, the link between its gene expression and phenotype remains unclear. RNA-seq analysis of 58 DCM samples and 12 publicly available control samples unveiled about 25,000 transcripts. A principal component analysis highlighted a distinct DCM-control separation. WGCNA revealed four transcriptome modules strongly associated with DCM. The purple module, which is the DCM-related module, was enriched with fibrosis-related genes and showed FSTL3 as a pivotal DCM-associated gene.

overall_design:
Right ventricular septal biopsies were obtained. DCM biopsies transcriptome data were compared with non-failing left ventricular samples (n=12) previously published datasets that are publicly available in the NCBI Gene Expression Omnibus (GEO) database from GSE11625.
Re-analysed Samples PRJNA477855:
Ctrl_1 GSM3219559 SAMN09484150 SRX4297607
Ctrl_2 GSM3219560 SAMN09484149 SRX4297608
Ctrl_3 GSM3219561 SAMN09484148 SRX4297609
Ctrl_4 GSM3219562 SAMN09484147 SRX4297610
Ctrl_5 GSM3219563 SAMN09484145 SRX4297611
Ctrl_6 GSM3219564 SAMN09484144 SRX4297612
Ctrl_7 GSM3219565 SAMN09484143 SRX4297613
Ctrl_8 GSM3219566 SAMN09484142 SRX4297614
Ctrl_9 GSM3219567 SAMN09484141 SRX4297615
Ctrl_10 GSM3219568 SAMN09484139 SRX4297616
Ctrl_11 GSM3219569 SAMN09484138 SRX4297617
Ctrl_12 GSM3219570 SAMN09484137 SRX4297618

first: Reo

last: Hata


title: Rice Chromatin Protein OsHMGB1 Is a Transcriptional Facilitator that Regulates Phosphate Homeostasis and Plant Growth [ChIP-seq]

summary:
Although phosphorus is one of the most important essential elements for plant growth and development, the epigenetic regulation of inorganic phosphate (Pi) signaling is poorly understood. In this study, we identified the high-mobility-group protein OsHMGB1 as a key regulator of phosphate homeostasis and plant growth in rice (Oryza sativa). OsHMGB1 expression is induced by Pi starvation and encodes a nucleus-localized protein. Relative to wild-type plants, Oshmgb1 mutant plants had lower Pi content in their leaves, whereas plants overexpressing OsHMGB1 had higher Pi content, indicating that OsHMGB1 positively regulates Pi accumulation. Transcriptome deep sequencing and chromatin immunoprecipitation followed by sequencing showed that OsHMGB1 regulated the expression of a series of phosphate starvation responsive (PSR) genes by binding to their promoters. Furthermore, Assay for Transposase-Accessible Chromatin followed by sequencing revealed that OsHMGB1 was involved in maintaining chromatin accessibility. Indeed, OsHMGB1 occupancy positively correlated with genome-wide chromatin accessibility and gene expression levels. Notably, we determined that OsHMGB1 interacted with RNA polymerase II to help regulate transcription, especially under low Pi conditions. Taken together, our results suggest that OsHMGB1 functions as a transcriptional facilitator, revealing a key epigenetic mechanism to regulate Pi homeostasis and fine-tune plant acclimation responses to Pi-limited environments.
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for HMG-GFP transgenic plants

overall_design: Yan,Wang


title: Rice Chromatin Protein OsHMGB1 Is a Transcriptional Facilitator that Regulates Phosphate Homeostasis and Plant Growth [RNA-seq i]

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Oshmgb1 mutans and wild-type (WT) plants under HP (high Pi, 200μM) and LP (low Pi, 200μM) conditions.


title: Rice Chromatin Protein OsHMGB1 Is a Transcriptional Facilitator that Regulates Phosphate Homeostasis and Plant Growth [ATAC-seq]


title: H3K4me3 ChIP-seq of C57BL/6 mouse embryonic stem cells with folate deficiency

city: Shanxi

first: wenbin

last: ren

address: 56 Xinjian South Road, Yingze District, Taiyuan City

institute: Shanxi Medical University

summary: In order to investigate whether folate deficiency affects histone H3K4me3 enrichment and then affecting the activity of Wnt signaling pathway, we performed ChIP-seq of H3K4me3 on folate-free embryonic stem cells and normal embryonic stem cells, respectively. Our sequencing data provides a new theoretical basis for the effect of folate on histone modification.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone variants H3K4me3 (Cell Signaling Technology; catalog number: 9751s; lot number: 14.)

first: Wenbin

last: Ren

first: Jianting

last: Li

first: Lu

first: Zhihua

last: Cao


title: A Titin Missense Variant Causes Atrial Fibrillation

status: Public on Dec 08 2025

city: Chicago

first: Mahmud

middle: Arif

last: Pavel

email: gmmahmud@uic.edu, arvindsr@uic.edu

state: Illinois

address: 840 South Wood Street, Suite 920S

department: Medicine/Cardiology

institute: University of Illinois at Chicago

summary: A single TTN point mutation- a missense variant ( TTN-T32756I) can impair sarcomere integrity and lead to atrial electrical remodeling, increasing AF- A link that needs investigation

overall_design: We performed an unbiased global transcriptomic analysis by RNA sequencing (RNA-Seq) separately on TTN WT and TTN-T32756I- hiPSC-aCMs.


title: CTDP1 governs a unique RNAPII phospho-form and coordinates Mediator recruitment, transcription efficiency, and splicing

city: Beijing

first: Dexun

last: Ji

state: Beijing

address: Haidian District, Beijing Summer Palace Road No. 5

department: School of Life Sciences

institute: Peking University

summary: We previously reported that the RNA polymerase II (Pol II) subunit RPB7 interacts with the phosphatase CTDP1 to regulate transcription termination-reinitiation. Here, we demonstrate that CTDP1 specifically dephosphorylates a unique phospho-isoform of Pol II, which is modified at tyrosine 1, serine 5, and serine 7 (Tyr1, Ser5, Ser7) of its C-terminal domain. Functionally, this regulation is critical for the recruitment of the Mediator complex to chromatin and for modulating Pol II transcriptional efficiency. Furthermore, by integrating phosphoproteomic and immunoprecipitation-mass spectrometry data, we show that CTDP1 also regulates the phosphorylation of numerous RNA splicing factors. Consequently, depletion of CTDP1 disrupts gene expression oscillations, leading to increased intron retention and aberrant splicing of cassette exons. These findings suggest that CTDP1 serves as a key integrator of transcription and splicing, potentially contributing to the regulation of circadian rhythms and the cell cycle.

overall_design: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing

first: Haonan

last: Zheng

first: Yuanhan

last: Sui

first: Qiqin

last: Xu


title: Primate gut microbiota induce evolutionarily salient changes in mouse neurodevelopment

city: Bethesda

first: Alex

last: DeCasien

state: MD

address: 9000 Rockville Pike

department: LNG

institute: National Institute on Aging

summary: Multiple primate species, including humans, evolved brains that are exceptionally large relative to their body sizes. These large brains coevolved with metabolic adaptations that enhance cerebral energy supply, including increased circulating glucose levels. While the gut microbiota (GM) is known to influence host metabolism, its potential role in primate brain evolution remains unclear. To investigate this, we inoculated germ-free mice with the GMs of primate species selected to separate the effects of brain size (encephalization) from phylogenetic relatedness: humans (large-brained, Catarrhini), macaques (smaller-brained, Catarrhini), and squirrel monkeys (large-brained, Platyrrhini). We first show that differences in brain gene expression between mice inoculated with human versus macaque GMs resemble those observed between actual human and macaque brains. Comparing the effects of the different primate GMs on mouse brain gene expression further revealed that, despite greater evolutionary distance, the GMs from the two larger-brained species (humans and squirrel monkeys) similarly upregulated genes associated with energy production. Notably, human GMs specifically increased the expression of genes involved in oxidative phosphorylation, and these gene expression changes correlated with increased abundances of GM metabolic pathways related to glucose metabolism and gluconeogenesis. Human GMs also downregulated evolutionarily conserved genes implicated in neurodevelopmental disorders such as autism. Although these are findings based on a small sample of primate species and must be interpreted as preliminary, they suggest that species differences in GM composition can influence brain metabolism and raise the possibility that the GM could have played a supporting role in primate encephalization.

overall_design: Bulk brain RNAseq data: 11,359 detectably expressed genes (excluding ribosomal genes) from the infralimbic/prelimbic frontal cortices (FC; corresponding to areas 25 and 32, respectively) of N=32 mice that were inoculated with the GMs of humans (Homo sapiens; N=12), squirrel monkeys (Saimiri boliviensis; N=8), or macaques (Macaca mulatta; N=12).

first: Jacob

last: Arnoff

first: Elizabeth

last: Mallot

first: Sahana

last: Kuthyar

first: Sriram

last: Chitta

first: Brian

last: Layden

first: Maria

last: Savo Sardaro

first: Stanton

last: Grey

first: Lawrence

last: Williams

first: Emma

last: Leichty

first: Hyo

last: Lee

first: Won

first: James

last: Curly

first: Christopher

last: Kuzawa

first: Katherine

last: Amato


title: CD51 expression delineates functionally distinct astrocyte subpopulations in neural circuits

city: Houston

first: Akdes

last: Serin Harmanci

state: TX

address: One Baylor Plaza

institute: Baylor College of Medicine

summary: Astrocytes execute a diverse range of tasks that facilitate brain physiology, raising the possibility that these diverse astrocytic roles are enabled by functionally distinct subtypes1,2. Recent studies identified molecular diversity amongst astrocytes3, however whether this molecular heterogeneity reflects specialized astrocyte subpopulations with distinct functions remains unknown. Leveraging prior molecular and functional studies4, we generated a CD51-FLP mouse line that enables the direct comparison of functional properties between CD51+ and CD51- astrocyte subpopulations in neural circuits in vivo. Here we show that CD51+ and CD51- astrocytes are endowed with unique morphological, physiological, and developmental properties in both the cortex and hippocampus. Functional studies demonstrate that CD51+ astrocytes selectively promote synapse formation in the developing cortex and circuit plasticity in the hippocampus. Mechanistically, we found that CD51+ astrocytes function through glypican 6 to promote synapse formation in the cortex, while CD51 itself drives circuit plasticity in the hippocampus. Applying these findings to brain injury, we found that exploiting the unique properties of CD51+ astrocytes promotes functional recovery after stroke through enhanced synaptic remodeling. Taken together, our studies identify specialized astrocyte subpopulations that exhibit distinct functional properties in the developing, mature, and injured brain.

overall_design: Cortex and hippocampus were dissected from CD51-Flp; Rosa-CAG-FSF-tdTomato mice and tdTomato+/GFP+ (CD51+ astrocytes) and tdTomato-/GFP+ (CD51- astrocytes) were FACS isolated. RNA was extracted from FACS isolated populations and prepared for RNA-sequencing.

first: Michael

last: Williamson

first: Junsung

last: Woo

first: Benjamin

last: Deneen


title: Response of gingival keratinocytes challenged with Selenomonas sputigena

city: Richmond

first: Daniel

last: Miller

state: Virginia

address: 1101 E. Marshall St. Sanger Hall 5-009

institute: Virginia Commonwealth University

summary: NanoString nCounter analysis using the human Host Response Panel was used to determine the expression of 618 genes involved in host response to infection from telomerase immortalized gingival keratinocytes (TIGKs) incubated with the oral pathogen Selenomonas sputigena ATCC 35185 compared to untreated control cells.

overall_design:
RNA was collected from 3 biological replicates from both the untreated control group and the S. sputigena treated group. The entire experiment was performed in duplicate, yielding 6 total samples from each treatment group. For treated cells, they were infected with 100 bacteria per TIGK cell for 4 hrs before RNA was isolated.
All samples were analyzed using the nCounter Host Response Panel to determine the expression of 618 human genes.

middle: P


title: Identification of genomic features that uniquely impact estrogen receptor alpha binding and its effects on gene expression in endometrial cancer

city: Salt Lake City

first: Alexandra

last: Richey

state: UT

address: 2000 Cir of Hope Dr

department: Biomedical Engineering

institute: University of Utah

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

overall_design: Refer to individual Series


title: Self-Organizing Neural Networks in Organoids Reveal Principles of Forebrain Circuit Assembly

city: Santa Cruz

first: Hunter

last: Schweiger

state: California

address: 2300 Delaware

institute: UCSC Genomics Institute

summary: The mouse cortex is a canonical model for studying how functional neural networks emerge, yet it remains unclear which topological features arise from intrinsic cellular organization versus sensory input. Mouse forebrain organoids provide a powerful system to investigate these intrinsic mechanisms. We generated dorsal (DF) and ventral (VF) forebrain organoids from mouse pluripotent stem cells and tracked their development using longitudinal electrophysiology. DF organoids showed progressively stronger network-wide correlations, while VF organoids developed more refined activity patterns with enhanced small-world topology and increased modular organization. Both organoid types form small-world networks, but their topological organization differs. These differences emerged without extrinsic inputs and correlate with Pvalb+ interneuron enrichment in VF organoids. Our findings demonstrate how cellular composition influences neural circuit self-organization, establishing mouse forebrain organoids as a tractable platform to study cortical network architecture.

overall_design: Single cell RNA sequencing was performed on 30 mouse cortical organoids from three separate cell lines (10 organoids per cell line).

first: Sebastian

last: Hernandez

first: Mohammed

last: Mostajo-Radji


title: BACH2 regulates T cell lineage states to enhance CAR T cell function [ATAC-seq]

city: St. Louis

first: Nathan

last: Singh

address: 660 S Euclid Ave

institute: Washington University School of Medicine in St Louis

summary: Nearly all chimeric antigen receptors (CARs) signal in the absence of antigen, referred to as “tonic signaling”. Tonic signaling of CARs containing the CD28 costimulatory domain has been shown to driveT cell exhaustion; in contrast, we found that tonic signaling of 41BB-containing CARs enhances T cell function. Using a panel of CARs targeting CD22, we identified that tonic 41BB signaling activatesBACH2, a transcriptional regulator that directs stem and memory programs. Overexpression of BACH2 prevented tonic CD28-driven exhaustion but locked CAR T cells in quiescent states. To overcome this, we linked BACH2 to a degradation domain and found that tuning BACH2 expression enhanced long-term efficacy of exhaustion-prone CAR T cells targeting liquid and solid tumors. Through interrogation of CAR products, we also found an association between BACH2 activity and clinical outcomes in patients with leukemia. These data identify a central role for BACH2 in regulating CAR T cell efficacy.

overall_design: ATAC-seq of primary human CAR T cells. Four different CARs targeting CD22 were sequenced (CD28 or 4-1BB-costimulatory domain with CD3z stimulatory domain. scFvs contain a Long (L) or Short (S) linker). BBs(BACH2 KO) denotes 4-1BB costimulatory domain, short linker, and CRISPR knockout of BACH2. All samples in technical triplicate.

first: Tien-Ching

last: Chang

first: John

last: Warrington


title: Escape from X inactivation is directly modulated by Xist non-coding RNA [Capture Hi-C]

city: Solna

first: Jasper

last: Panten

address: Tomtebodavägen 23

institute: SciLifeLab

summary: X-chromosome inactivation silences one copy of the X-chromosome in female cells, but a number of genes escapes this inactivation. Increased levels of Xist RNA, the molecular actor driving X-inactivation, results in silencing of escaping genes. To address how chromosome topology responds to changes in transcriptional activity of escapees, we performed allele-specific Capture Hi-C analysis of clusters of escaping genes on the inactive X chromosome in NPCs. We performed the experiments after 7 and 21 days of Xist induction and upon washout of doxycycline and in presence or absence of Xist’s partner SPEN. We further tested changes in the 3D topology of regions surrounding known constitutive escapees in ESCs upon increased Xist levels.

overall_design: TX1072.G4 first generation hybrid mouse ESCs (from a C57BL6/J x CAST/EiJ cross) were cultured and clonal neural progenitor cell lines were generated from them by in vitro differentiation. All NPC cell lines carry an inactive B6 X chromosome and a doxycycline-inducible transgene on the Xi. Allele-specific Capture Hi-C was performed to characterized the 3D spatial organization of the two X chromosomes in ESC at two regions containing known constitutive escapees (Kdm5c and Kdm6a) and in two NPC lines, E6 and CL30.7, of two clusters of genes that escape X-inactivation (Kdm5c and Hcfc1-Mecp2).

first: Edith

last: Heard

first: Agnese

last: Loda

first: Antonia

last: Hauth

first: Nicolas

last: Servant


title: Delineating the role of co-stimulatory signals on human virus-specific memory CD8+ T cell activation and expansion using highly selective T cell receptor-targeted biologics

city: Bronx

first: Harris

last: Goldstein

state: NY

address: 1300 Morris Park Avenue

department: Pediatrics

institute: Albert Einstein College of Medicine

summary: To delineate the minimum signals required to activate and expand antigen-specific memory CD8+ T cells, we recapitulated the discrete activation signals delivered by antigen-presenting cells using antigen-specific T-cell receptor-specific biologics termed Immuno-STAT (IST), which can specifically deliver a T cell receptor (TCR) signal alone or paired with a defined co-stimulatory signal to antigen-specific CD8+ T cells. Using a reductionist approach that provides defined TCR and co-stimulatory signaling, we demonstrated that different IST could engage TCR alone or in combination with either CD28 or 4-1BB to initiate distinct transcriptional programs in memory CMV-specific CD8+ T cells. As compared to activation by TCR signaling alone, the combination of TCR and CD28 or 4-1BB co-stimulatory signals significantly altered the transcriptome and drove expression of genes related to growth and survival. Nevertheless, TCR signaling in the presence of IL-2 (5 U/ml) was sufficient for robust recall activation and expansion of functional cytomegalovirus CMV(NLV)-specific and HIV(SL9)-specific memory CD8+ T cells. This response contrasts with naïve CD8+ T cells, which required CD28 co-stimulation in addition to TCR stimulation for antigen-specific activation and expansion even in the presence of high levels of IL-2 (100 U/ml). These results have important implications for antigen-specific immunotherapy by indicating that biologics that deliver TCR signals alone in the presence of IL-2 may be sufficient for immunotherapeutic strategies designed to expand memory CD8+ T cells to eliminate cancerous or infected cells. In contrast, strategies that aim to stimulate naïve T cell responses may benefit from the codelivery of TCR and CD28 signals.

overall_design: To understand the transcriptional response of CMV-specific memory CD8 T cells to TCR-stimulation with or without CD28 or 4-1BB co-stimulation, human PBMC were stimulated with a pMHC-based TCR agonist linked to either a CD28 or 4-1BB agonist. After stimulation, CMV-specific CD8 T cells were collected using FACS and RNA was isolated. Replicates were samples of PBMC from the same donor that underwent treatment, cell sorting, RNA isolation, and sequencing independently. Samples that received no treatment or retreatment were used as controls.

first: Christopher

last: Hiner

first: Hong

last: Hur

first: April

last: Mueller

first: Manoj

last: Kandpal


title: Identification of genomic features that uniquely impact estrogen receptor alpha binding and its effects on gene expression in endometrial cancer [CRISPRScreen]

first: Alexandra

last: Richey

summary: Estrogen receptor alpha (ER) is an established oncogenic transcription factor in breast and endometrial cancer; however, more is known about the mechanisms controlling ER behavior in breast cancer, and therapies targeting ER have only been successful in breast cancer patients. To address this disparity, we sought to identify genomic features that control ER in endometrial cancer and determine to what extent these factors differ from those in breast cancer. We focused on the locations of estrogen response elements (EREs), ER’s preferred DNA binding motif, throughout the human genome. To identify factors that predict ER genomic binding and effects on target gene expression, we applied machine learning to genomic data for each ERE in Ishikawa cells (ER+ endometrial cancer) and T-47D cells (ER+ breast cancer). Many of these factors, such as chromatin accessibility and histone modifications, were predictive of ER activity in both cell lines. However, the transcription factors that predict ER activity were found to be cell type-specific, including FOXA1 and GATA3 in T-47D cells, and ETV4 and SOX17 in Ishikawa cells. In addition, the features that predict ER binding and effects on gene expression differed, with transcription at EREs in the absence of estrogen being predictive of regulatory activity.  To verify our findings in the Ishikawa cells, we performed a CRISPR knockout screen, which confirmed the discovery that SOX17 controls ER activity in endometrial cancer cells. These results identify important genomic features of ER binding and regulatory activity and how they differ between endometrial cancer and breast cancer cells.

overall_design: CRISPR KO was used to study which epigenetic and transcription factors affect ER activity in Ishikawa cells

first: Jason

last: Gertz

first: Noel

last: Kitchen


title: Identification of genomic features that uniquely impact estrogen receptor alpha binding and its effects on gene expression in endometrial cancer [SOX17_ChIPseq]

overall_design: SOX-17 ChIP-seq was performed in Ishikawa cells in the absence of estrogen and other hormones.

first: Craig

last: Rush


title: Whole transcriptome analysis in obstetric antiphospholipid syndrome

city: Jinan

first: Lan

last: Zhang

address: jingsi

institute: Shandong University

summary: This study aims to investigate the expression profiles of coding and non-coding RNA in OAPS, thereby deepening our understanding of the potential mechanisms of OAPS. Plasma samples were collected from 3 OAPS patients and 3 healthy controls. Then, exosomes were separated by differential ultracentrifugation. The transcriptome of purified exosomes was comprehensively analyzed using the Illumina sequencing platform. Exosomal messenger RNA (mRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) were identified using a threshold of |log2 (fold change)| ≥ 1 and P < 0.05.


title: Single-cell RNA-seq of endothelial and pericyte populations in the mouse cochlear stria vascularis

city: Portland

first: Xiaorui

last: Shi

address: 3250 SW Sam Jackson Park Rd

department: OHRC

institute: Oregon Health & Sciences Univers

summary: The cochlear stria vascularis (SV) maintains the endocochlear potential and relies on specialized vascular endothelial cells and pericytes. To characterize the transcriptional profiles of these vascular populations at single-cell resolution, we performed single-cell RNA sequencing (scRNA-seq) on SV tissue from reporter mice. SV was microdissected from temporal bones of 1–3 month-old Tie2-GFP (endothelial reporter) and NG2-DsRed (pericyte reporter) mice, enzymatically dissociated to obtain single-cell suspensions, and, when applicable, subjected to FACS enrichment for Tie2-GFP–positive endothelial cells or NG2-DsRed–positive pericytes. Viable cells were loaded onto the 10x Genomics Chromium platform for single-cell capture and 3′ barcoded library preparation. This dataset contains two independent batches corresponding to SV endothelial cell–enriched and pericyte-enriched preparations and enables analysis of vascular heterogeneity within the mouse stria vascularis.

overall_design: Two independent single-cell RNA-seq batches from the 1-3 months mouse cochlear stria vascularis were isolated by Fluorescence-activated cell sorting (FACS) and analyzed using scRNA-seq. Batch 1. Endothelial cell–enriched batch (Tie2-GFP) Batch 2. Pericyte-enriched batch (NG2-DsRed)

first: Zhiqiang

last: Hou

first: Yunpei

first: Jinhui

first: Pingting

last: Wang


title: BACH2 regulates T cell lineage states to enhance CAR T cell function [Cut & Run]

first: Nathan

last: Singh

overall_design: CUT&RUN of primary human CAR T cells with an antibody against cJUN. Two different CARs targeting CD22 were sequenced (CD28 or 4-1BB-costimulatory domain with CD3z stimulatory domain. scFvs contain a Short (S) linker). 28s+BACH2 denotes CD28 costimulatory domain, short linker, and BACH2 over expression vector. All samples in technical triplicate.

first: Tien-Ching

last: Chang

first: John

last: Warrington


title: In vivo CRISPR screening identifies SAGA complex members as a key regulators of hematopoiesis [ChIP]

city: Philadelphia

first: Michael

last: Haney

address: 422 Curie Boulevard

institute: University of Pennsylvania, Perelman School of Medicine, Department of Pathology

summary: The biological mechanisms that sustain the vast blood production required for healthy life remain incompletely understood. To search for novel regulators of hematopoiesis, we performed a genome-wide in vivo hematopoietic stem and progenitor cell (HSPC)-based CRISPR knockout screen for regulators of hematopoiesis. We discovered SAGA complex members, including Tada2b and Taf5l, as key regulators of hematopoiesis. Loss of Tada2b or Taf5l strongly inhibited hematopoiesis in vivo, causing a buildup of immature hematopoietic cells in the bone marrow. The SAGA complex deposits histone H3 lysine 9 acetylation (H3K9ac) and removes histone H2B ubiquitination (H2Bub). Loss of Tada2b led to reductions in H3K9ac levels and altered H2Bub enrichment in HSPCs, implicating disruption of SAGA complex activity. This was associated with upregulation of interferon pathway genes, reduced mitochondrial activity, and increased megakaryocyte progenitor cell commitment. Loss of these factors also enhanced the cell outgrowth and the interferon pathway in an in vivo human myelodysplastic syndrome cell line model. In summary, this study has identified the SAGA complex as an important regulator of hematopoiesis.

overall_design: ChiP-seq of HSPCs in vitro including Tada2b KO HSPCs

first: Adam

last: Wilkinson

first: Leonid

last: Olender


title: Host sex effect on Brugia pahangi

city: Baltimore

first: Julie

last: Dunning Hotopp

address: 670 W Baltimore St

institute: University of Maryland, Baltimore

summary: This study addresses the effect that the sex of the mammalian host, Meriones unguiculatus, has on the filarial nematode, Brugia pahangi

overall_design: RNA-Seq analysis of Brugia pahangi worms (adult males, adult females, microfilariae) isolated from either male or female gerbils. The gerbils were infected either using the intraperitoneal (IP) or subcutaneous (SQ) infection routes

first: Christopher

last: Holt

first: Robin

middle: E

last: Bromley

first: Benjamin

last: Sparklin

last: Mattick

first: Jeremy

last: Foster

first: Michelle

last: Michalski


title: Heat-Shock Pathway Activation by TRC-051384 Protects Spiral Ganglion Neurons from Noise-Induced Hearing Loss [Spatial Transcriptomics]

first: Jeffrey

last: Savas

address: 303 E. Chicago Avenue, Ward 12-013

department: Neurology

institute: Northwestern University

summary: Noise-induced hearing loss (NIHL) is a major public health problem caused by damage to cochlear hair cells, synapses, and spiral ganglion neurons (SGNs). However, effective treatments are completely lacking. We investigated cellular stress responses induced by loud noise in a mouse model of cochlear synaptopathy and tested whether selective activation of the dominant pathway identified could confer protection. RNA sequencing and spatial transcriptomics revealed that noise exposure elicited a robust but transient upregulation of endoplasmic reticulum chaperones and proteasome subunits in SGNs and supporting cells. To target this response, we administered TRC051384, a small-molecule activator of the heat shock transcription factor Hsf1, prior to noise exposure. TRC051384 crossed the blood–labyrinth barrier and reached the cochlea, induced heat shock protein gene expression, and restored ubiquitin–proteasome function in SGNs. Notably, TRC051384 treatment improved auditory brainstem response recovery, preserved Wave I amplitudes, and maintained ribbon synapse density. These findings establish proteotoxic stress in SGNs as a central driver of NIHL and identify HSF1 activation as a promising therapeutic strategy.

overall_design: Spatial transcriptomics using GeoMx was performed on cochlear tissue from 16-week-old CBA/CaJ mice subjected to acoustic overexposure. Mice were divided into two groups (N = 5 per groups): Control – mock-exposed (no noise). Noise-exposed,2 hours of 100 dB SPL broadband noise and sacrificed immediately after exposure.

middle: N

first: Seby

last: Edassery

first: Miguel

last: Ramirez


title: In vivo CRISPR screening identifies SAGA complex members as a key regulators of hematopoiesis [CRISPR]

overall_design: CRISPR KO screening in HSPCs

first: Haney

last: Michael

first: Archana

last: Shankar


title: Combined inhibition of HRAS and MEK induces tumor regression and restores myogenic differentiation in HRAS-mutant rhabdomyosarcoma

last: Considine

state: Maryland

address: 550 North Broadway

institute: Johns Hopkins University

summary: Hyperactive RAS signaling drives tumorigenesis in PAX 3/7::FOXO1 fusion-negative rhabdomyosarcoma (FN-RMS). Despite the frequency of these mutations, indirect RAS pathway-directed therapies have been ineffective for RAS-driven RMS. Farnesyltransferase (FTase) inhibitors (FTIs), such as tipifarnib, inhibit HRAS membrane localization and blunt HRAS effector signaling, leading to an antitumor effect in HRAS-mutant FN-RMS preclinical models. Response to FTase inhibition is limited by adaptive feedback reactivation of ERK signaling and upregulation of wild-type (WT) RAS. We found that the combination of HRAS suppression with FTI and MEK inhibition (MEKi) impaired ERK reactivation and reduced ERK transcriptional output in HRAS-mutant RMS models. Co-targeting FTase and MEK restrained tumor progression and induced terminal myogenic differentiation. These findings highlight an effective combinatorial strategy and support its preclinical translation for patients with HRAS-mutant RMS.

overall_design: RNA-sequencing of FN-RMS cell cells following siRNA RAS knockdown or treatment with small molecule inhibitors of RAS pathway constiuents.

first: Patience I

last: Odeniyide

first: Alyza

last: Skaist

first: Elana

last: Fertig

first: Christine A

last: Pratilas


title: Exposure of equne monocytes to parasite antigens and phytochemicals

city: Frederiksberg C

first: Andrew

last: Williams

address: Dyrlægevej 100

country: Denmark

institute: University of Copenhagen

summary: Cinnamaldehyde and carvacrol modulated gene expression induced by parasite antigen in monocytes, with an upregulated of an antioxidant defense network

overall_design: Monocytes were isolated from fresh equine blood, and exposed to either LPS, helminth (cyathosomin) antigen, or antigen combined with either cinnamaldhyde or carvacrol


title: Restores Epithelial Identity and Mitigates Lung Fibrosis

city: Austin

first: Qi

last: Tan

state: MN

address: 801 16th Ave NE

department: The Hormel Institute

institute: Univesity of Minnesota

summary: In this study, we investigated how S100A2 overexpression, hypoxic stress, and 2D monolayer culture conditions disrupt the epithelial identity of human iPSC-derived alveolar type 2 cells (iAT2s), a key pathological feature of lung fibrosis. Using defined perturbations, we examined how each factor contributes to cellular reprogramming, loss of AT2 fate, and induction of stress-responsive or basal-like transcriptional states. Together, these analyses provide mechanistic insight into how microenvironmental and molecular cues drive AT2 cell dysfunction during fibrotic remodeling.

overall_design: We analyzed six experimental groups of iAT2 cells subjected to distinct perturbations to model AT2 cell stress and plasticity: 1. iAT2 normoxia control 2. iAT2 under hypoxia 3. iAT2 control 4. iAT2 with S100A2 overexpression 5. iAT2 cultured in 2D monolayer conditions 6. iAT2 transitioned from 2D monolayer back to 3D culture This design allowed us to compare how molecular overexpression, environmental stress, and loss of 3D niche cues individually and collectively influence AT2 epithelial identity.


title: Single-nucleus RNA-seq reveals reprogrammed hepatocytes that express c-Met/β-catenin oncogenes in LPD-fed mice.

city: New Brunswick

first: Xinlu

last: Han

address: 164 Frelinghuysen Road Piscataway

institute: Rutgers university

summary: To further interrogate the impact of low protein diet (LPD) on the c-Met/β-catenin expressing hepatocytes, we performed single-nucleus RNA-sequencing (snRNA-seq) analysis. Mice were fed on chow diet (CD) or LPD for one week, followed by SB-HTVI of c-Met/β-catenin. Two weeks post SBHTVI, 42,277 single nuclei were sequenced with 12,413 in the CD-vector control, 10,225 in CD c-Met/β-cat, 9,707 in LPD-vector control, and 9,932 in LPD c-Met/β-cat.

overall_design: Bl/6 mice were fed with CD or LPD for one week, then injected with c-Met/β-catenin plasmids via SB-HTVI, and kept on the same diets for two more weeks.

first: Jiekun

last: Yang

first: Junrong

last: Yan


title: H3K4me3 ChIP-seq profiling of mouse prefrontal cortex after chronic social defeat stress

city: Novosibirsk

first: Natalya

last: Bondar

address: 10, Ac. Lavrentieva ave.

country: Russia

institute: Institute of Cytology and Genetics SB RAS

summary: Stress-induced mental disorders, including depression and anxiety disorders, constitute a global issue in contemporary society due to treatment complexity and the diversity of manifestations. Understanding the molecular mechanisms of these disorders presents a significant challenge for neurobiology. We investigated the effects of social defeat stress (SDS) of varying durations (10 and 30 days) on behavioral patterns and the H3K4me3 landscape in the prefrontal cortex of C57BL/6 mice. Furthermore, we compared these data with previously published H3K4me3 landscape data obtained after 15 days of SDS and transcriptomic data collected after 10, 15, and 30 days. We discovered that a 30-day period of stress results in more pronounced depressive-like behavior. SDS induces slight alterations in the H3K4me3 density across numerous nucleosomal peaks. The analysis of differential enrichment peaks of H3K4me3 in promoter regions following varying durations of SDS revealed that the aggregation of multiple H3K4me3 nucleosome peaks in the promoter region functions as a QR code, likely affecting the promoter's state regarding the accessibility of transcription factors. Furthermore, we identified a cluster of genes in the promoter regions exhibiting differential enrichment peaks of H3K4me3 following SDS of any duration. This cluster includes genes encoding transcription factors such as Mef2c and Nr4a3, as well as postsynaptic density proteins (Shank2, Shank1, and Gria2), which are associated with stress sensitivity and the onset of depression; their protein products are involved in synaptic transmission and signal transduction mechanisms. The comparison of ChIP-seq and RNA-seq data following varying durations of SDS stress enabled a deeper insight intothe dynamics of SDS-induced changes. Together, these findings understanding of the molecular mechanisms of SDS in the prefrontal cortex.

overall_design: H3K4me3 ChIP-seq of prefrontal cortex from adult male C57BL/6J mice subjected to 10-day or 30-day social defeat stress, and unstressed controls.

first: Natalia

first: Vasiliy

last: Reshetnikov

first: Polina

last: Ritter

first: Nikita

last: Ershov

last: Zhukova

first: Semyon

last: Kolmykov

first: Tatiana

last: Merkulova


title: Biop-C enables genome-wide detection of balanced and unbalanced rearrangements in preimplantation human embryos

last: Torgunakov

address: Prospekt Lavrentyeva 10

institute: Institute of Cytology and Genetics

summary: Preimplantation genetic testing for structural rearrangements (PGT-SR) is critical for embryo selection. Most advanced PGT-SR platforms rely on sequence- or marker-based analysis near chromosomal breakpoints, which is costly, labor-intensive, and time-consuming. As a result, clinical practice often defaults to using PGT-A, a platform that cannot detect balanced rearrangements affecting the offspring's reproductive potential. In this study, we introduce Biop-C, a Hi-C–based technique enabling the comprehensive detection of both unbalanced and balanced translocations, including Robertsonian ones, as well as copy number variations (CNV). By developing custom algorithms for translocation detection, we achieved high accuracy in embryo and biopsy samples. We show that using machine-learning-based approaches allows detecting CNVs using low-coverage Hi-C without control euploid human embryos, which are typically unavailable. In a cohort of 88 samples for translocation detection and 78 samples for CNV detection, Biop-C correctly identified over 86% of detected translocations, and 83% of these calls were concordant with the refined reference. Additionally, Biop-C confirmed the aneuploid status in 84% of embryos, with no embryos initially classified as euploid by standard PGT being misclassified as aneuploid. For CNVs, Biop-C detected 72% of reference CNVs, and 95% of all identified CNVs were true positives. Notably, Biop-C identified an unbalanced translocation in an embryo derived from a couple with a previously undiagnosed parental translocation, demonstrating its diagnostic value. We had 36 samples derived from patients carrying balanced chromosomal rearrangements, we identified 4 balanced translocations in samples classified as These findings establish Biop-C as a powerful PGT-SR approach for distinguishing between normal and balanced embryos, with significant implications for embryo selection and genetic counseling in IVF.

overall_design:
Biop-C is a Hi-C–based technique, which enables detection of chromosomal abnormalities in preimplantation embryos. In total, we prepared the Biop-C libraries from 120 samples (47 embryos and 73 biopsy samples), fixed using the ConA-bead protocol, or using the in-drop method.

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Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
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first: Yana

last: Stepanchuk

first: Andrey

last: Popov

first: Alexey

last: Ivanov

first: Eduard

last: Chuyko

first: Olga

last: Kanbekova

first: Alsu

last: Saifitdinova

first: Anna

last: Kinunen

first: Elizaveta

last: Nevskaya

last: Pavlova

first: Maria

last: Sherba

first: Denis

last: Pyankov

first: Anastasia

last: Kirillova

first: Svetlana

last: Avdeichik

first: Irina

last: Zvereva

first: Daria

last: Panchenko

first: Yuri

last: Vyatkin

last: Slepukhina

first: Mikhail

last: Pomaznoi

first: Dmitry

last: Shtokalo

first: Pavel

last: Orlov

last: Subbotovskaya

first: Oxana

last: Ryzhkova

last: Zhigalina

first: Nikolay

last: Skryabin

first: Ivan

last: Gaziev

first: Anton

last: Buzdin

first: Igor

last: Lebedev

last: Gridina

first: Veniamin

last: Fishman


title: Identification of an IRF–ZBP1–caspase-8–NINJ1 axis in driving PANoptosis and pathology during alcohol-associated liver disease.

city: Memphis

first: Thirumala-Devi

last: Kanneganti

state: Tennessee

address: 262 Danny Thomas Pl

department: Immunology

institute: St. Jude Children's Research Hospital

summary: Alcohol-associated liver disease (ALD) is a chronic inflammatory condition in which the innate immune pathways driving liver injury are not fully defined. In this study, we used clinical liver and serum samples, together with mouse models of ALD, to investigate the role of the innate immune sensors in disease pathogenesis. We observed increased ZBP1 expression in patients with ALD, with levels correlated with disease progression. Ethanol exposure induced ZBP1-dependent inflammatory cell death (PANoptosis) in both immune cells (including macrophages, monocytes, and Kupffer cells) and non-immune cells (hepatocytes). Basal ZBP1 expression was upregulated by the interferon regulatory factors IRF1 and IRF9, and ZBP1 activation engaged a PANoptotic pathway, where caspase-8 was a central regulator; the cell death was executed by NINJ1-mediated membrane rupture, independent of gasdermin D, gasdermin E, and MLKL. In ALD mouse models, Zbp1-deficient animals were significantly protected from liver injury and pathology. ZBP1 and NINJ1 expression were also elevated in liver and serum from patients with ALD, supporting their potential as disease biomarkers. Together, these data define an IRF–ZBP1–caspase-8–NINJ1 axis as a key driver of inflammatory cell death in ALD and a potential target for therapeutic intervention.

overall_design: RNA-Seq profiling of wild-type BMDMs and Irf9 KO BMDMs at 0 hrs (control) and 3 hrs after ethanol treatment.

first: Qiang

last: Qin

first: Wen

last: Chen

first: Clay

last: King

first: Sivakumar

last: Kumar

first: Chadi

last: El Farran

first: Peter

last: Vogel

first: Rebecca

last: Tweedell


title: Hypothalamic CRH Neuronal Activation Triggers Splenic Cell Proliferation and Promotes Atherosclerosis

city: Guiyang

first: Li

last: Li

address: No. 50, East Shicheng Road

institute: Guizhou University of Traditional Chinese Medicine

summary: The development of atherosclerotic plaque in the arterial intima can cause cardiovascular and cerebrovascular diseases worldwide. Our previous study reported that widespread neuroimmune cardiovascular interfaces appeared in the adventitia of atherosclerotic plaque, establishing a structural artery-brain circuit. Hypothalamic corticotropin-releasing hormone (CRH) neurons play a pivotal role in regulating the stress response and peripheral neuro-immune response. However, it remains unclear whether hypothalamic CRH neurons can regulate atherosclerosis. Elevated levels of sympathetic neurotransmitters and immune cells in the blood of patients with myocardial infarction suggested a role for sympathetic nervous activation in validating and promoting immune cell proliferation. Activation of hypothalamic CRH neurons in ApoE knockout mice promoted atherosclerosis and adventitial inflammation. Single-cell immune repertoire sequencing analysis demonstrated that hypothalamic CRH neurons drove splenic Treg/Teff imbalance via the ADRβ2-MAPK axis and reshaped immune interaction networks to promote early atherosclerotic inflammation. Cell proliferation labeling experiments proved that hypothalamic CRH neurons promoted splenic immune cell proliferation in the early stage of atherosclerosis. Stereotaxic injection of apoptotic viruses to eliminate hypothalamic CRH neurons and surgical ablation of splenic sympathetic signals reduced splenic immune cell proliferation and inflammatory responses, which contributing to the alleviation of atherosclerosis. In summary, our study demonstrates that hypothalamic CRH neurons triggered splenic cell proliferation and promoted atherosclerosis.

overall_design: ApoE knockout mice subjected to either high-fat diet alone or high-fat diet combined with chronic restraint stress for 6 weeks. Single-cell suspension of spleen was obtained and analyzed using scRNA-seq.

first: Jing

last: Xie

first: Xin

last: Wang

first: Tao-tao


title: Bulk RNA-seq of the CD and LPD-fed mice injected with vector control or c-Met/ΔN90-β-catenin by SB-HTVI

first: Xinlu

last: Han

summary: We performed bulk RNA-seq to compare liver tissues from 4 groups of mice: vector control fed with CD, c-Met/β-cat mice fed with CD, vector control fed with LPD, and c- Met/β-cat mice fed with LPD. Differential gene expression and gene set enrichment analyses (GSEA) were performed and identified two clusters that might help explain the differential tumor development in the CD and LPD groups.

overall_design: Vec and c-Met/ΔN90-β-catenin fed with CD or LPD (n=3 in each group) were harvested at the endpoint of the CD-fed c-Met/ΔN90-β-catenin mice.

first: Zong

last: Wei-Xing

first: Shen

last: Jianliang

first: Yan

last: Junrong


title: Profiles and roles of N6-methyladenosine modification in bovine oocyte maturation [MeRIP]

city: Hefei

first: TC

last: H

address: 130 Changjiang West Road

institute: AAU

summary: The quality of bovine oocytes is crucial for in vitro embryo production technology, thus it is essential to study the mechanisms of oocyte maturation. N6-methyladenosine (m6A) modification plays a key role in gametogenesis and embryonic development. However, the dynamic landscape and functional roles of m6A modification during bovine oocyte maturation remain unclear. We conducted transcriptome-wide m6A landscape analysis on bovine oocytes at the GV and MII phases using MeRIP-seq and RNA-seq technologies. We identified a total of 6,323 differential m6A peaks in the two groups of oocytes, with 4,422 m6A peaks being significantly upregulated and 1,901 m6A peaks significantly downregulated. The combined analysis of MeRIP-seq and RNA-seq identified 262 genes with significant differences in both methylation modification and transcriptome levels. GO and KEGG enrichment analyses of these genes revealed significant enrichment in biological processes and signaling pathways such as endocytosis, thermogenesis, ribosome, cellular metabolism, Apelin signaling pathway, and HIF-1 signaling pathway. Finally, we examined the roles of m6A modification in bovine oocyte maturation. The results showed that inhibition of m6A modification affects nuclear and cytoplasmic maturation of oocytes. Our results reveal the m6A modification profile during bovine oocyte maturation. Furthermore, we found that inhibition of m6A modification leads to meiotic failure. These results provide a theoretical basis for studying the function of RNA modification in oocyte maturation.

overall_design: GV stage and MII stage bovine oocytes cultured in vitro were collected for MeRIP-seq and RNA-seq

first: Tiancang

first: Zhichao

first: Xinqi

last: Gan

first: Zhiyuan

last: Yang

first: Wenzhuo

first: Kunlong

last: Hu

first: Ruiqing

last: Zhu

first: Yunsheng

first: Yunhai

last: Zhang

first: Zubing

last: Cao


title: Bulk liver tissue RNA-seq was performed using the vector control livers and that with c-Met/ΔN90-β-catenin SB-HTVI for 2 and 3 weeks

summary: Bulk RNA-seq of the liver tissues at early time points after c-Met/β-catenin expression (2 and 3 weeks) showed changes of gene expression of cell growth/migration, carbohydrate metabolism, and lipid metabolism.

overall_design: Seven-week-old GS WT male mice were injected with vehicle or c-Met/ΔN90-β-catenin/SB10 plasmids, and livers were harvested 0, 2 or 3 weeks after the injection for RNA-sequencing analysis.


title: Rice Chromatin Protein OsHMGB1 Is a Transcriptional Facilitator that Regulates Phosphate Homeostasis and Plant Growth

city: Hangzhou

address: 866 Yuhangtang Road, Xihu District, Hangzhou City, Zhejiang Province, China

institute: Zhejiang University

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

overall_design: Refer to individual Series


title: Bulk RNAseq data of white matter tissue injury

city: Suzhou

first: kaici

last: Tang

address: Renailu 199

institute: Soochow University

summary: We compared the transcriptomic responses in the mouse white matter tissue drive white matter lesions following LPC- and L-NIO-induced injury.

overall_design: 1.Bulk RNA sequencing: The injured and contralateral tissues were isolated from the corpus callosum at 4 days after LPC-induced repair injury or L-NIO-induced WMS. The corpus callosum tissue collected from the sham-operated mice served as a control. In brief, total RNA was extracted via TRIzol reagent and quantified, after which ribosomal RNA depletion and poly(A) purification were performed. Libraries were quantified and pooled for paired-end sequencing on an Illumina NovaSeq 6000 platform. 2.Single-cell RNA sequencing: The injured and contralateral tissues were isolated from the corpus callosum at 4 days after LPC-induced repair injury or L-NIO-induced WMS. The corpus callosum tissue collected from the sham-operated mice served as a control. The tissue samples were sent for single-cell high-throughput sequencing (scRNA-seq) via the 10× Genomics platform. Briefly, viable single-cell suspensions (> 90% viability) were loaded onto microfluidic chips to generate gel bead-in-emulsions (GEMs), where cellular mRNA was barcoded and reverse transcribed. Amplified cDNA underwent fragmentation, adapter ligation, and library construction according to the manufacturer's protocol. High-throughput sequencing was performed via the Illumina NovaSeq 6000 platform to obtain high-quality transcriptome data.

first: Yu

first: Kaici

first: Hongli

first: Hongbo

last: Mi

first: Hao


title: Human microphysiological systems of aging recreate the in vivo process expediting evaluation of anti-gerontic strategies

city: Berkeley

first: Yuchen

last: He

address:
344 Morgan Hall, University of California
 Berkeley

department: Department of Nutritional Science and Toxicology

institute: University of California Berkeley

summary: The search for biological mechanisms of human aging is stalled by a lack of suitable models and it remains unknown whether, and to what degree, rejuvenation reported in rodents translates to people. Here we report a hiPSC-derived microphysiological system modelling the white adipose tissue-liver axis in the presence of heterochronic human serum to study aging and rejuvenation in humans. We reveal changes in functional and molecular hallmarks of aging and rejuvenation, and we investigate unknown biomarkers and mechanisms of plasticity in human tissue aging as well as potential rejuvenation strategies. The microphysiological chip recapitulates, in 4 days, aging-associated hallmarks that occur after decades of aging in people, including gerontic shifts in gene expression and oxidative DNA damage.  We uncover unknown signaling networks in human aging, knock-on effects of aging in fat on liver, sexual polymorphisms of aging, tissue memory of age, and develop a custom machine learning model for biological age. Combining heterochronic human serum with the microphysiological system allows for rapidly establishing human tissue aging, discovering clinically relevant mechanisms, biomarkers, and testing of anti-gerontic approaches.

overall_design: To investigate the effect of human serum from old and young donors on Liver-MPS, we performed RNA-seq using RNA extracted from Liver-MPS perfused with old circulatory milieu (OCM) and young circulatory milieu (YCM). Further, to investigate knock-on effects of aged white adipose tissue on liver aging, we performed RNA-seq using RNA extracted from Liver-MPS connected with OCM/YCM pre-treated WAT-MPS.

first: Lin

last: Qi

first: Alexandra

last: Sviercovich

first: Xiaoyue

last: Mei

first: Erzhen

last: Chen

first: Yihan

last: Xia

first: Michael

middle: J

last: Conboy

first: Irina

first: Andreas

last: Stahl


title: Inhibition of the cancer stem cell immune checkpoint SOAT1 suppresses regulatory T cell functions through a trans-cellular 20(S)-Hydroxycholesterol-GPR132 pathway in mice.

city: shanghai

first: wanqi

last: fang

address: jiangwan

institute: fudan

summary: SOAT1 (sterol O-acyltransferase 1) serves as a cancer stem cell-specific immune checkpoint that facilitates trans-cellular signaling through the release of 20-Hydroxycholesterol (20-OHC) and subsequent activation of GPR132 on regulatory T cells (Tregs). This pathway plays a crucial role in modulating the tumor immune microenvironment and can significantly influence the balance between immune activation and suppression. In the context of cancer, SOAT1 is instrumental in regulating the cholesterol metabolism of cancer stem cells. When SOAT1 is inhibited, there is an increase in the secretion of 20-OHC by tumor cells. This oxysterol not only functions as a signaling molecule but also acts as a ligand that binds to GPR132, a G protein-coupled receptor primarily expressed on immune cells, including Tregs. This binding triggers a cascade of intracellular signaling pathways that ultimately enhances the immunosuppressive functions of Tregs. Mechanistically, the activation of GPR132 by 20-OHC leads to downstream signaling events that may involve pathways such as JAK-STAT and PKC signaling, promoting the development and survival of Tregs while enabling them to exert their immunosuppressive effects within the tumor microenvironment. This results in the downregulation of effector T cell activities and impairs the maturation and activation of dendritic cells (DCs), which are pivotal for effective anti-tumor immune responses. The presence of Tregs, particularly in elevated frequencies within tumors, can contribute to an immunosuppressive environment that protects cancer cells from immune-mediated destruction. Thus, the SOAT1-20OHC-GPR132 axis represents a critical mechanism through which cancer cells can evade immune surveillance. By controlling cholesterol metabolism through SOAT1, tumors can manipulate the availability of 20-OHC, amplifying the immunosuppressive capacity of Tregs and facilitating an environment conducive to tumor growth and progression. Targeting SOAT1 and the associated 20-OHC signaling pathway may offer a promising therapeutic strategy to neutralize Treg-mediated immunosuppression. Inhibiting SOAT1 not only disrupts the tumor's ability to produce 20-OHC but also potentially reprograms the immune landscape, promoting a more activated and effective anti-tumor immune response. Overall, SOAT1's dual role as a cancer stem cell-specific immune checkpoint and its involvement in the trans-cellular signaling of 20-OHC make it a valuable target for innovative cancer immunotherapies aimed at enhancing immune recognition and attack on cancer cells.

first: Yahui

last: Ding