title: Transcriptomic analysis of the planktonic growth of Streptococcus pneumoniae serotype 1 reveals serotype-specific gene regulation

city: Dublin

first: Karsten

last: Hokamp

state: Dublin

address: Stephen's Green

department: Genetics

country: Ireland

institute: Trinity College Dublin

summary: Streptococcus pneumoniae is an opportunistic pathogen that colonizes the mucosal surfaces of the human upper respiratory tract. To the exception of very few studies, all previous transcriptomic analyses on the pneumococcus were carried out using lab-adapted strains such as D39 or TIGR4. Our study is one of the first to investigate the transcriptomes of serotype 1 (S1) pneumococci. We took the most basic approach of growing S. pneumoniae in brain heart infusion medium using three distinct strains, i.e. sequence type ST306, ST217 and ST615, as representative isolates of the European, African and South American S1 clusters. As a follow-up to our recent studies on these three lineages, we sought to investigate their respective in vitro transcriptomic profiles in comparison to D39. In total, 292 genes showed significant differential expression in the exponential growth phases of all three S1 isolates compared to D39. A total of 151 genes showed higher transcription levels while 141 genes presented lower expression. The most prominent functional groups showing higher expression included the competence pathway and purine metabolism, while lactose metabolism and iron/amino acid transport presented lower expression in serotype 1 strains. Our study provides novel insight into the signature gene expression associated with hypervirulent pneumococci S1 and highlight the need to perform transcriptomic analysis on pneumococcal strains other than lab-adapted strains.

overall_design:
To investigate the Streptococcus S1-specific transcriptional profile we carried out RNA-seq on three S1 strains and one S2 strain over different growth stages and compared the exponential phase samples.

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The table below lists GEO accessions reused/reanalyzed for this study.
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first: Pongchaikul

last: Pisut

first: Hokamp

last: Karsten

first: Yahya

last: Reham

first: Bricio-Moreno

last: Laura

first: O'Brien

last: Marie

first: Kadioglu

last: Aras


title: The Maternal Gut-Immune Axis Programs the Neuroimmune Landscape of the Developing Brain [snATAC-seq]

status: Public on Jul 11 2025

city: Boston

first: Brian

last: Kalish

state: MA

address: 220 Longwood Ave

department: Neurobiology

country: USA

institute: Boston Children's Hospital

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We performed single nucleus ATAC-seq from male and female E12.5 embryonic mouse brians.

overall_design: Single nucleus ATAC seq from embryonic brain at E12.5 of males and female mice.

first: Bharti

last: Kukreja

first: Shin

last: Jeon

first: Wuxinhao

last: Cao

first: Bianca

last: Rusu

first: Camille

middle: F

last: Harrison

first: Shahrzad

last: Ghazisaeidi

first: Allison

last: Loan

first: Nareh

last: Tahmassian

first: Shiyao

last: Ning

first: Min

middle: Y

last: Feng

first: Jing

last: Wang

first: Shreya

last: Padhy

first: Yeong

middle: S

last: Yim

middle: T


title: PoreMeth2: decoding the evolution of methylome alterations with Nanopore sequencing. [RNA-seq, WGS]

city: Florence

first: Marta

last: Baragli

address: Via di S. Marta 3

department: Department of Information Engineering

country: Italy

institute: University of Florence

type: Expression profiling by high throughput sequencing

summary: In epigenetic analysis, identifying differentially methylated regions (DMRs) typically involves detecting groups of consecutive CpGs that show a significant change in their average methylation level. However, the methylation state of a genomic region can also be defined by a mixture of patterns (epialleles) with variable frequencies and the relative proportion of such patterns can provide information on its mechanisms of formation. However, traditional methods based on bisulfite conversion and NGS, due to the read size (150 bp), allow epiallele frequency analysis only in high-CpG-density regions, limiting differential methylation studies to only 50% of the entire human methylome. Nanopore sequencing, with its long reads, enables the analysis of epiallele frequency across both high- and low-density CpG regions. We introduce a novel computational approach, PoreMeth2, an R library that integrates epiallelic diversity and methylation frequency changes from Nanopore data to identify DMRs, assess their formation mechanisms and annotate them to genic and regulatory elements. We applied PoreMeth2 to cancer and glial cell datasets, demonstrating its ability to distinguish epigenomic changes with strong effect on gene expression from those with weaker effect on transcriptional activity. PoreMeth2 is publicly available at https://github.com/Lab-CoMBINE/PoreMeth2.

overall_design: For WGS: Methylation analysis before and after 48 hours treatment with a G-protein coupled receptor agonist. For RNA-seq: Quadruplicate (HPGC) RNA seq experiments before and after treatment and subsequent gene expression quantification.

first: Gianluca

last: Mattei

first: Barbara

last: Gega

first: Alessandra

last: Mingrino

first: Martina

last: Chiechia

first: Gianmaria

last: Frigè

first: Luca

last: Mazzarella

first: Francesco

last: De Logu

first: Romina

last: Nassini

first: Pier Giuseppe

last: Pelicci

first: Alberto

last: Magi


title: Elevated synaptic PKA activity and abnormal striatal dopamine signaling in Akap11 mutant mice, a genetic model of schizophrenia and bipolar disorder [bulkSeq]

city: Cambridge

first: Ally

last: Nicolella

address: 75 Ames St

department: Stanley Center for Psychiatric Research

institute: Broad Institute

summary: Loss-of-function mutations in AKAP11 (a protein kinase A (PKA)-binding protein) greatly increase the risk of bipolar disorder and schizophrenia. To determine the neurobiological functions of AKAP11 and the consequences of its absence, we conducted multi-omic analyses of Akap11 mutant mouse brains. We find that AKAP11 is a key regulator of PKA proteostasis in the brain whose loss leads to dramatically elevated PKA expression and phosphorylation, especially in synapses. Transcriptomic analysis shows extensive gene expression changes throughout the brain, including prominent decreases in synapse-related genes sets. Gene expression is especially affected in spiny projection neurons of the striatum, a brain region implicated in motivation, cognition and psychiatric disorders. In vivo, real-time measurements of PKA activity in ventral striatum of Akap11-/- mice revealed constitutively elevated kinase activity, which distorts dopamine to PKA signaling. Our work reveals the molecular basis of circuit dysfunction in a genetically valid model of psychotic disorder.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from prefrontal cortex (PFC), somatosensory cortex (SSC), hippocampus (HP), striatum (ST), Thalamus (TH) and substantia nigra (SN) at 4, and12  weeks of age in Akap11 mutant mice.

first: Song

last: Bryan

first: Nicolella

last: Ally


title: Anti-PD-L1 antibodies exacerbate arthritis and pain via increased production of CXCL8/IL-8 and FGF9 in synovial fibroblasts

city: TOKYO

first: HITOSHI

last: TOYODA

address: 1-5-8 Hatanodai

country: Japan

institute: SHOWA UNIVERCITY

summary: Immune checkpoint inhibitors (ICIs) in cancer therapy are challenged for immune-related adverse events (irAEs), such as inflammatory arthritis induced by ICI therapy (ICI-arthritis) and exacerbation of rheumatoid arthritis (RA). As well as activating T cells by inhibiting programmed cell death protein 1 (PD-1)/ programmed death ligand 1 (PD-L1) signal, anti-PD-L1 antibody (αPD-L1 ab) activate intracellular pathway through PD-L1 binding. However, the effects of αPD-L1 ab on synovial fibroblasts, which are important in the pathogenesis of arthritis, are unknown.

overall_design: To assess the effect of αPD-L1 ab on synovial fibroblasts, fibroblast-like synoviocytes (RA-FLS) were collected from two RA patients and stimulated with tumor necrosis factor (TNF)-α. The cells were then stimulated with αPD-L1 ab (BioXCell) or Ctrl IgG for 24 h and total RNA was collected. The obtained total RNA was subjected to RNA-seq to examine gene expression comprehensively.

first: Hitoshi

last: Toyoda

first: Masahiro

last: Hosonuma

first: Ryota

last: Nakano


title: Mucor circinelloides strain:CBS172.27 or 1006PhL or CBS277.49 | isolate:PS15+ or PS14 or PS10 Raw sequence reads from H3K9me2 and RNAP ChIP experiments

city: Murcia

first: Carlos

last: Pérez-Arques

state: Murcia

address: Campus Universitario Espinardo, Facultad de Biología

department: Genética y Microbiología

country: Spain

institute: Universidad de Murcia

summary: ChIP-seq data for three Mucor spp. from the Mucor circinelloides species complex: PS15, PS14, and PS10. ChIP was performed against H3K9me2 and RNA polymerase II (RNAP). PS10 and PS14 include samples from a wild type (WT) and an epimutant strain (E1 and E3, respectively), while PS15 include a WT from each mating type (- and +), two epimutant strains (E1m, E10p) and their progeny (#10 and #34, respectively)

overall_design: ChIP-seq was performed on epimutants and naive wildtype strains to determine the role of H3K9me2-based heterochromatin in epimutation, and the transcriptional activity using RNA polymerase II occupancy as a proxy.

first: María Isabel

last: Navarro-Mendoza

first: Joseph

last: Heitman


title: Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol synthesis and storage

city: New York

first: Genomics-core-facility

last: WCM

state: New York

address: 1300 York Ave

institute: Weill Cornell Medicine

summary: Cholesterol performs multiple essential roles in cells. Enhanced cholesterol synthesis and storage in lipid droplets have been linked to cancer aggressiveness, particularly in lipid-rich and hormone-sensitive cancers such as prostate cancer . Cholesterol anabolism and catabolism are finely regulated in tumor cells in response to various nutritional states. Mitochondria have increasingly been recognized as a signal transduction organelle, particularly concerning metabolites derived from mitochondrial activity. The link between mitochondrial regulation and cholesterol synthesis remains inadequately understood. Here, we show that propionyl-CoA promotes cholesterol synthesis, storage, and further progression in prostate cancer cells. We found that propionyl-CoA, mainly produced by isoleucine and valine metabolism in the mitochondria, can translocate through the mitochondrial membrane and serves as a substrate for modifying cleaved SREBP2, stabilizing it and thereby promoting cholesterol synthesis and storage in lipid droplets. This process facilitates cancer metastasis and castration resistant partially through enhancing androgen synthesis in prostate cancer cells. Our results demonstrate that branched-chain amino acid (BCAA) catabolism and propionate metabolism in mitochondria are involved in the regulation of cholesterol synthesis and utilization through metabolite-mediated protein modification. We anticipate that our findings provide a critical link between amino acid metabolism and cholesterol anabolism, highlighting a mechanism that plays a crucial role in the development of castration resistance in prostate cancer patients. This study offers a theoretical rationale for targeting the production of propionyl-CoA, particularly through the metabolism of isoleucine and valine, as an effective strategy to inhibit cholesterol synthesis and its related diseases.

overall_design: PCCA was knocked down in the LNCaP human prostate cancer cells. Total mRNA was extracted from the cells for the RNA-seq analysis to compare the gene expression pattern induced by PCCA knocking down.

first: Zhongchi

last: Li

first: John

last: Blenis


title: Multiple intron motifs have redundant functions in trans-splicing of the mod(mdg4) locus

city: Moscow

first: Maxim

last: Tikhonov

address: Vavilova

department: Regulation of Genetic Processes

country: Russia

institute: Institute of Gene Biology RAS

summary: In contrast to canonical cis-splicing, trans-splicing combines exons from two distinct transcripts, yielding chimeric mRNAs. This process is typically suppressed through the tight coupling of pre-mRNA synthesis and splicing, primarily due to the inherent risk of generating chimeric proteins with aberrant or deleterious properties. Nevertheless, trans-splicing permits the creation of a substantially greater diversity of mRNA isoforms that encode variants of a single protein. One compelling example is the mod(mdg4) locus in Drosophila, where all mRNAs, encompassing over 30 isoforms, are exclusively generated via trans-splicing, which integrates common constitutive exons with one of several alternative 3′ variable exons transcribed from independent promoters. This investigation analyzed the roles of the mod(mdg4) gene’s promoter, exons, and introns in trans-splicing. Our methodology involved a previously validated model in the heterogeneous 22A genomic region, augmented by targeted deletions within the fourth intron of the endogenous locus. We determined that the mod(mdg4) promoter only modestly enhances trans-splicing efficiency. Critically, the predominant determinants are multiple, redundant RNA-binding protein motifs concentrated within the proximal 412 bp of the fourth intron. These results collectively support a model wherein trans-splicing is primarily mediated by redundant intronic motifs recognized by spliceosome components.

overall_design: RNA-seq experiments were performed on whole 2–3 day-old adult male Drosophila from the wild-type control line y[1]w[1118] and the mod(mdg4)[c13] mutant line, in which an intronic fragment spanning positions 225–553 was deleted and only the c13 motif was integrated. Total RNA was extracted and enriched by hybridization with a biotinylated probe targeting constitutive exons to increase the proportion of reads mapping to the locus of interest. Changes in trans-splicing patterns across all isoforms were compared between the control and mutant lines.


title: miRNA microarray expression from glioblastoma & astrocytes under 100V/m 48hr dcEF stimulation & sham

city: Taoyuan

first: Hsieh-Fu

last: Tsai

state: Taiwan

address: E0408, no.259 Wenhua 1st road

country: Taiwan

institute: Chang Gung University

summary:
Direct current electric field mimicking a physiological electrical field from transepithelial potential difference can direct cell migration (electrotaxis)and cellular signaling. While the transcriptome in dcEF has been reported and more studied, the miRNA expression of cells under dcEF stimulation is less understood.
We use a reversibly sealed dcEF stimulation bioreactor to apply uniform dcEF to glioblastoma cell lines and primary astrocytes and investigate if dcEF can induce differential expression of  cellular miRNA and exosomal miRNA expression that can regulate the gene expression

overall_design: Cells were cultured in the the bioreactor prior to assembly in a physioxia (5%CO2, 5%O2) environment. The bioreactor was assembly submerged in 1X PBS to avoid bubble entrapment and then 100V/m dcEF was applied for 48hours. The conditioned medium containing the exosome was collected and isolated for exosomal RNA. Cellular total RNA was also extracted. Duplicated DNA are tagged and pooled. Then 130ng of RNA of cellular RNA and exosomal RNA were hybridized in miRNA 4.0 microarray. RMA+DABG with normalization and human only miRNA analysis was performed.

first: Amy

middle: Q

last: Shen


title: Gene expression profiling of developing ovine embryonic fat tail tissues across nine stages (from E50 to E80) at single cell level

first: Jiangang

last: Han

address: 59 Donnybrook Manor, Dublin 4

institute: University College Dublin

summary: In mammals, whit adipose tissue (WAT) acts as the primary energy reservoir to modulate glucose and lipid homeostasis, and can also intervene several aspects of organismal physiology by endocrine manor. Hypertrophic development of WAT is associated with various metabolic disease, but hyperplastic adipogenesis is more responsible for metabolic health and distinct metabolic response across depots. However, our understating for cellular origins of adipocytes, the hierarchy of adipogenic progenitor population and the crucial regulons governing adipogenesis remains uncompleted. In this study, by constructing global gene expression and chromatin accessibility profiling for developing ovine fat tail tissue covering the whole stage of adipogenesis at single cell resolution, we identified several causal genes promoting adipogenesis and three cellular origins promising the congenital, repaid and massive fat deposition, including one progenitor and stem cell population (MCM5+/SFRP4+), two connective tissue progenitor clusters (COL6A6+/ALDH1A1+), and one vascular smooth muscle cell population (GUCY1B1+/RAI14+). Meanwhile, we also systemically investigated causal genes driving the dynamic specialization of angiogenesis, osteogenesis, chondrogenesis and myogenesis that accompanying fat tail development. Furthermore, by comprehensive integration of scRNA-seq and scATAC-seq data, we deciphered the enhancer-driver gene regulation networks (eGRNs) underpinning each lineage specialization in an unbiased manner. Collectively, our study broadens the understating for progenitor population hierarchy, enriches the available specific markers for various cell types, and provides new insights into cellular origins of adipocytes and molecular mechanism underpinning dynamic differentiation processes of multi lineages.

overall_design: The embryonic ovine tail tissues at E50, E55, E60, E63, E66, E69, E72, E75 and E80 were used to make single cell suspension and perform scRNA-seq, one replicate each time point. Sheep breed, Tan sheep, a kind of fat tailed sheep.

first: Lin

last: Jiang

first: Yuehui

last: Ma

first: David

last: MacHugh


title: CRISPR screens identify EXO1 as a therapeutic target for cancers with Fanconi anemia pathway and BRCA1-A complex deficiencies [PM20138]

city: London

first: Simon

middle: J

last: Boulton

address: Midland Road

country: United Kingdom

institute: The Francis Crick Institute

summary: EXO1 is a conserved multi-functional exonuclease that performs roles in mismatch repair, homologous recombination, nucleotide excision repair, translesion DNA synthesis, resection of stalled replication forks and processing of Okazaki fragments. However, EXO1 loss is well tolerated, suggesting the existence of compensatory mechanisms that could be exploited therapeutically in DNA damage repair (DDR) deficient cancers. Using CRISPR screening, we find that EXO1 loss is synthetic lethal with many somatically inactivated DDR genes identified as frequent vulnerabilities in cancers, including Fanconi anemia (FA) pathway and BRCA1-A complex genes. We also identify the spliceosome factor and tumour suppressor ZRSR2 as synthetic lethal with loss of EXO1 and show that ZRSR2-deficient cells are attenuated for FA-pathway activation, exhibiting cisplatin sensitivity and radial chromosome formation, which we attribute to discreet splicing defects that compromise FA pathway genes. Finally, we show that vulnerabilities caused by mutations in FA or ZRSR2 genes depend on the catalytic activity of EXO1 and can be further sensitised in combination with either PARP inhibitors or ionising radiation. Altogether, we establish the rationale for development of EXO1 inhibitors for treatment across a broad spectrum of cancers with distinct DDR vulnerabilities, which are not effectively targeted with current therapeutic approaches.

overall_design: To investigate synthetic lethal interactions with EXO1 loss, we performed a genome-wide CRISPR-Cas9 dropout screen. Wild type and EXO1 KO cell lines were transduced with Brunello library from Addgene containing sgRNAs targeting 19114 genes, with 4 sgRNAs per gene, and with 1000 non-targeting sgRNAs. Transductions (performed in a biological triplicate on cells that were passaged separately through expansion) were achieved through transduction of 100 x 10^6 cells in 12 well plates at MOI of 0.4 for 500x representation of each sgRNA (titer required for both cell lines was determined prior to experiment). Cells with viruses were spun at 290 x g for 90 minutes at 37 degrees. The following day cells were trypsinised to transfer into 5-layer flasks and puromycin was added for selection. 40 x 10^6 cells for each replicate was passaged onwards every two days to ensure that sgRNA representation is maintained. Replicates were then treated with doxycycline (1ug/ml final concentration) for 6 days. Samples were collected at day 6 and day 16 for library preparation and sequencing (harvesting 60 x 10^6 cells per sample). Genomic DNA was extracted with the PureLink Genomic DNA Mini Kit (Invitrogen; 16 columns per sample). 200ug gDNA was used for PCRs with Ex Taq polymerase (TaKaRa) to prepare sgRNA amplicon libraries following Broad Institute’s protocol with P5 mix of oligos and barcoded P7 oligos. Libraries (sgRNA amplicons) were gel purified with QIAquick Gel Extraction Kit (QIAGEN), followed by MinElute PCR Purification kit (QIAGEN) for buffer exchange, and analysed with Agilent 2100 Bioanalyzer.

first: Marija

last: Maric

first: Harshil

last: Patel


title: CRISPR screens identify EXO1 as a therapeutic target for cancers with Fanconi anemia pathway and BRCA1-A complex deficiencies [PM22329]

overall_design: To investigate drivers of synthetic lethal interactions between EXO1 and FANCG or EXO1 and ZRSR2, we performed genome-wide CRISPR rescue screens. eHAP iCas9 EXO1 KO cells, that were previously transduced with Brunello library in triplicate for the dropout screen and frozen, were recovered and transduced with lenti-sgRNA-Hygro with sgRNAs for either FANCG or ZRSR2 or non-targeting control (at MOI of 1 based on predetermined titer). Transduced cells were selected with hygromycin and Cas9 expression was induced with doxycycline. Cells were passaged every 2-3 days (keeping 40 x 10^6 cells representation) and samples were collected 10 days after Cas9 expression induction. Genomic DNA was extracted with the PureLink Genomic DNA Mini Kit (Invitrogen; 16 columns per sample). 200ug gDNA was used for PCRs with Ex Taq polymerase (TaKaRa) to prepare sgRNA libraries following Broad Institute’s protocol with P5 mix of oligos and barcoded P7 oligos. Libraries (sgRNA amplicons) were gel purified with QIAquick Gel Extraction Kit (QIAGEN), followed by MinElute PCR Purification kit (QIAGEN) for buffer exchange, and analysed with Agilent 2100 Bioanalyzer.

first: Tyler

last: Stanage


title: CRISPR screens identify EXO1 as a therapeutic target for cancers with Fanconi anemia pathway and BRCA1-A complex deficiencies

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

overall_design: Refer to individual Series


title: Molecular Cartography of the Human and Mouse Down Syndrome Brain [MERFISH]

first: Brian

last: Kalish

summary:
Given the importance of linking human and model system pathobiology, we also performed highly multiplexed RNA in situ spatial transcriptomics on a well-established trisomic mouse model (Ts65Dn) to study the cellular landscape of the trisomic brain during early life and aging. We profiled the spatial transcriptome of > 240,000 cells in the mouse brain and identified trisomy-associated gene expression patterns in  the molecular control of neurogenesis, gliogenesis, and myelination.
Multiplexed error-robust fluorescence in situ hybridization (MERFISH) was performed on postnatal day 0 (P0) and 6 month (6mo) euploid and trisomic (Ts65Dn) mice (n=3 per condition). Coronal sections of the entire brain were used for analysis.

overall_design: Min Yi, Feng

first: Wuxinhao

last: Cao

first: Gen

first: Bharti

last: Kukreja

first: Nareh

last: Tahmasian

first: Bianca

last: Rusu

first: Ji-Young

last: Youn


title: Molecular Cartography of the Human and Mouse Down Syndrome Brain [snRNA-seq]

summary: To gain molecular insight into the prenatal neurobiology of DS, we performed single-nucleus sequencing, spatial transcriptomics, and proteomics on mid-gestational prenatal human brain tissue. We captured altered expression dynamics of lineage commitment genes in DS neural progenitor cells, which suggest changes to the fate and functionality of neuronal and glial cells.

overall_design: We performed Slide-seq on mid-gestational prenatal human samples (n=3 euploid, n=3 Down Syndrome).

first: Min Yi

last: Feng

last: Li


title: Multiplex Epigenome Editing of MECP2 to Rescue Rett Syndrome Neurons [ChIP-Seq]

first: Xiaonan

last: Guan

state: NY

address: 1150 St Nicholas Ave, 403

institute: Russ Berrie Medical Science Pavillion

summary: Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by loss-of-function heterozygous mutations of MECP2. Reactivation of the silent wild-type MECP2 allele on the inactive X chromosome (Xi) represents a promising therapeutic opportunity for female RTT patients. Here, we applied a multiplex epigenome editing approach to reactivate MECP2 on Xi. Demethylation of the MECP2 promoter by dCas9-Tet1 with target sgRNA reactivated MECP2 on Xi in RTT hESCs without detectable off-target effects at the transcriptome level. Neurons derived from methylation edited RTT hESCs reversed the smaller soma size and electrophysiological abnormalities. Insulation of the methylation edited MECP2 locus in RTT neurons by dCpf1-CTCF with target crRNA stabilized MECP2 reactivation and rescued the RTT-related neuronal defects, providing a proof-of-concept study for multiplex epigenome editing to treat RTT.

overall_design: Identification of binding sites of dCas9-Tet1, CTCF and dCpf1-CTCF-HA

first: Junming

last: Qian

first: Charles

middle: H

first: Rudolf

last: Jaenisch

first: X

last: Liu


title: Multiplex Epigenome Editing of MECP2 to Rescue Rett Syndrome Neurons [ChIP-BS-Seq]

type: Methylation profiling by high throughput sequencing

overall_design: Evaluation of off-target effects by comparing DNA methylation level changes between dCas9-dTet1(dC-dT) and dCas9-Tet1(dC-T)


title: Multiplex Epigenome Editing of MECP2 to Rescue Rett Syndrome Neurons [RNA-Seq]

overall_design: Evaluation of off-target effects by comparing gene expression profiles of samples dCas9-dTet1(dC-dT) and dCas9-Tet1(dC-T)


title: Multiplex Epigenome Editing of MECP2 to Rescue Rett Syndrome Neurons


title: Integration of multiomics reveals the mechanism of Lycium barbarum polysaccharides inhibit MCF-7 cell proliferation

city: Ningxia

first: feng

middle: xu

last: fu

address: Shengli Street

country: China

institute: Ningxia Medical University

summary: Background：Breast cancer, as a highly prevalent malignant tumor among women, has a consistently high mortality rate due to metastasis and drug resistance. Lycium barbarum polysaccharides (LBP), which have been reported to have significant anti-tumor activity, have not yet had their molecular mechanism and signaling pathways against breast cancer clearly defined. Methods and Results：In this study, the CCK-8 assay determined that treatment with 8 mg/mL LBP for 48 h was the optimal condition for subsequent multi-omics analysis. The results demonstrated that a high concentration of LBP significantly reduced the viability of MCF-7 cells and inhibited cell proliferation. Transcriptome sequencing revealed that LBP markedly altered the expression levels of the genes HO-1, FTH1, FTL, and TFRC. Metabolomics analysis further indicated that LBP significantly impacted glutathione metabolism, glycerophospholipid metabolism, and the alanine-aspartate-glutamate metabolic pathway. Further integration of transcriptomic and metabolomic data suggests that LBP may suppress cell proliferation by activating the ferroptosis pathway via the NRF2/HO-1 axis. To further validate this hypothesis, we conducted additional experiments to detect the NRF2/HO-1 signaling pathway and markers associated with ferroptosis. The results demonstrated that LBP treatment significantly upregulated the expression of NRF2 and its downstream effector molecule HO-1. Moreover, the specific NRF2 inhibitor ML385 was able to reverse the alterations in GSH, Fe2+, and MDA levels induced by LBP. Conclusion：In conclusion, our research results indicate that LBP induces ferroptosis by activating the NRF2/HO-1 signaling pathway.

overall_design: RNA-seq profiling of MCF-7 cells and MCF-7 cells treated with LBP(8 mg/mL).

first: Li

middle: y

last: Ding

first: Yi

middle: t

last: Shang

first: Zhen

last: Zhang

first: Hong

last: Yang

first: Yu

last: Deng

first: Tian

last: He

first: Guo

middle: q

first: Jia

middle: x

last: Ma

first: Xu

middle: f

last: Fu

first: Xing

last: Du


title: Multiplex Epigenome Editing of MECP2 to Rescue Rett Syndrome Neurons [4C]

overall_design: Evaluation the off-target effects by comparing gene expression profiles of samples dCas9-dTet1(dC-dT) and dCas9-Tet1(dC-T)


title: To identify the differential expression of aGalcer/IL-2 treated T cells (iNKT) from human peripheral blood mononuclear cells  of healthy donors (HD), chronic hepatitis B (CHB) and HBV-infected hepatocellular cacinoma (HCC) patients

city: Wuhan

first: xiufang

last: weng

address: 13# Hangkong Rd, Wuhan, Hubei

institute: Huazhong University of Science and Technology

summary: To identify the different status of iNKT cells treated by aGalcer/IL-2 from CHB and HCC patients compared to HD. We enriched α-GalCer/IL-2 expanded iNKT cells from healthy donors (HD iNKT), CHB patients (CHB iNKT), and HBV-infected HCC patients (HCC iNKT) to rperforme next-generation sequencing (NGS).  Illumina mRNA-seq sample preparation kit was used to perform paired-end library sequencing with Illumina HiSeq 2000 and sequence analysis was determined using the Illumina data analysis pipeline. Based on the comparison results，we performed the GO and KEGG pathway enrichment analysis. That might suggest the different status of iNKT cells treated by aGalcer/IL-2 between HD, CHB and HBV-infected HCC patients.

overall_design: Differential gene expression between iNKT cells treated by aGalcer/IL-2 from HD, CHB and HBV-infected HCC patients.

first: Xiufang

last: Weng


title: RNAseq of Rpl18*-specific T cells from MC38 tumor and draining lymph node

status: Public on Jul 10 2025

city: Pittsburgh

first: Lawrence

middle: P.

last: Kane

state: PA

address: 5051 Centre Ave.

department: Immunology

institute: University of Pittsburgh

summary: The protein PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation and can play important roles in T cell differentiation. We have generated mice with CD8-specific TrIP deficiency. Here we provide data detailing that activated TrIP KO CD8 T cells display an increased inflammatory transcriptional profile in the absence of TrIP. Consistent with these effects, we also show that knockout of TrIP specifically in CD8 T cells resulted in reduced growth of syngeneic tumors. When characterizing the tumor-infiltrating cells, we found that TrIP KO led to an increase in the number of tumor-infiltrating T cells, as well as a delay in the acquisition of an exhausted phenotype, based on phenotypic and transcriptomic analyses. Finally, our data suggest that TrIP regulates the diversity of T cell clonal responses to tumors, since we observed an increase in the number of distinct T cell clonotypes responding to a tumor neoantigen. Taken together, we show that TrIP intrinsically restricts the CD8 T cell response to tumors, and that targeting TrIP may augment the anti-tumor response in a way that is distinct from established checkpoint therapies.

overall_design: Tumor and tumor draining lymph nodes (TDLN) from WT and CD8-specific TrIP knockout mice were harvested 10 days after MC38 tumor injection. CD8+ Rpl18 Tetramer+ cells were sorted from both tissues and prepared for sequencing.

first: Benjamin

middle: M

last: Murter

middle: P


title: PoreMeth2: decoding the evolution of methylome alterations with Nanopore sequencing.[RNA-Seq]

first: Marta

last: Baragli

overall_design: Triplicate RNA seq experiments and subsequent gene expression quantification of three AML patients at first diagnosis (tum) and after relapse (rel).

first: Gianluca

last: Mattei

first: Barbara

last: Gega

first: Alessandra

last: Mingrino

first: Martina

last: Chiechia

first: Gianmaria

last: Frigè

first: Luca

last: Mazzarella

first: Francesco

last: De Logu

first: Romina

last: Nassini

first: Pier Giuseppe

last: Pelicci

first: Alberto

last: Magi


title: Serdemetan enhances bone regeneration by coordinated regulation of osteoblast and osteoclast activity through the p53 pathway

city: Seoul

first: Sol

last: Jeong

address: Gwanakgu, Gwanakro1

country: South Korea

institute: SNU

summary: Serdemetan, an MDM2 inhibitor traditionally known for anticancer activity, demonstrates dual pro-osteogenic and anti-osteoclastic effects via p53 activation, showing bone regenerative efficacy comparable to alendronate in preclinical models.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
Comparative gene expression profiling analysis of RNA-seq data for Serdemetan treatment or control cells

Please note that paired-end R1/R2 reads for the hBMSC samples were analyzed separately as single-end dataset, resulting in 4 data columns in the hBMSC_read_count.csv.

first: Seung-Chan

last: An

first: Hyun-Ju

first: Sungjoon

last: Lim

first: Jin Man

last: Kim

first: Soonchul

last: Lee


title: TCRseq of Rpl18*-specific T cells from MC38 tumor and draining lymph node

first: Lawrence

last: Kane

first: Benjamin

last: Murter

first: Lawrennce


title: RNA sequencing of WT and TrIP KO P14 TCR Tg T cells stimulated in vitro

overall_design: Splenocytes from WT and CD8-specific TrIP knockout P14 mice were cultured for 24 hrs under 3 different conditions; Unstimulated (50 U/ml rIL-2 + 2 ng/ml rIL-12), Stimulated (100 ng/ml HiAff gp33 peptide + 50 U/ml rIL-2 + 2 ng/ml rIL-12), and stimulated + PI3Ki (10 μM IC87114 + 100 ng/ml HiAff gp33 peptide + 50 U/ml rIL-2 + 2 ng/ml rIL-12). After 24 hr stim., CD8 T cells were sorted out and bulk RNAseq was performed.


title: The human transcription factor occupancy landscape viewed using high-resolution in situ base-conversion strand-specific single-molecule chromatin accessibility mapping

city: Stanford

first: Georgi

middle: Kolev

last: Marinov

state: California

address: 279 Campus Drive West, Beckman Center, B-257A/259

institute: STANFORD UNIVERSITY

summary: Chromatin accessibility profiling is a key tool for mapping the location of cis-regulatory elements (cREs) in the genome and tracking chromatin state dynamics during development, in response to various external and internal stimuli, and in disease contexts. Single-molecule footprinting (SMF) methods that rely on the labeling of individual accessible DNA bases have emerged in recent years as a powerful chromatin accessibility mapping approach, as they provide not just an average readout of accessibility over a given genomic position but also the distribution of accessibility states within a population at the level of individual original DNA molecules. However, SMF approaches have been limited either in their resolution or in labeling readout accuracy. To address these limitations, we have developed a high-resolution strand-specific single molecule footprinting approach (C->U/T-ssSMF) based on the application of highly active sequence context-independent endogenous methylation-insensitive double-strand DNA (dsDNA) deaminases (CseDa01 and LbDa02), which convert accessible cytosines into uracils (and in turn into thymine after amplification). We demonstrate the application of the method to mapping fine-grained single-molecule accessibility states in human cell lines in both a short and a long-read format, and quantifying the occupancy states of individual transcription factors (TFs) as well as TF co-accessibility and strand-specific accessibility patterns.

overall_design: C->T-SMF in GM12878 cells

middle: K

first: William

last: Greenleaf


title: Transcriptome profiles of LAM cell models exposed to oleic acid

city: L'Hospitalet del llobregat

first: Miquel Angel

last: Pujana

state: Barcelona

address: Gran via 199, Hospital Duran i Reynals

department: ProCURE

institute: Catalan Institute of Oncology IDIBELL

summary: RNA-seq profiling of Tsc2-deficient mouse embryonic fibroblasts (MEFs) and TSC2-deficient 621-101 human angiomyolipoma cells exposed to oleic acid or basal condition.

overall_design: RNA-seq profiling of Tsc2-deficient MEFs and TSC2-deficient 621-101 cells cultured under basal conditions or treated with oleic acid. Each condition includes biological replicates.

first: Roderic

last: Espín


title: Comprehensive analysis of microRNA expression provides mechanistic insights into transcriptomic alteration in primary and metastatic testicular germ cell tumors

city: Baltimore

first: Taibo

last: Li

state: MD

address: 1830 E Monument Street, Suite 2-300

institute: Johns Hopkins School of Medicine

type: Non-coding RNA profiling by high throughput sequencing

summary: MicroRNA (miRNA) dysregulation is implicated in testicular germ cell tumor (TGCT) pathogenesis. Here, we characterized miRNA expression profiles across TGCT histologic subtypes using miRNA-sequencing on 43 formalin-fixed paraffin-embedded (FFPE) tissue samples (30 primary, 13 metastases) from 32 patients to identify diagnostic markers and their regulatory functions. From 20 seminomas (SEM), 14 non-seminomatous germ cell tumors (N-SEM), and 9 teratomas, we profiled a total of 2,606 miRNAs. Compared to teratomas, 154 miRNAs (targeting 657 genes) were enriched in SEM, and 141 miRNAs (targeting 358 genes) in N-SEM. miR-200-3p, targeting the DNA methyltransferase DNMT3B, was enriched in N-SEM versus SEM. Our findings showed high concordance with The Cancer Genome Atlas (TCGA)-TGCT data (Pearson R > 0.66, p < 1e-10). miRNA expression was largely similar between primary and metastatic tissues and between chemotherapy-treated and untreated teratomas, reflecting teratoma chemo-resistance. Using novel candidates, miRNA-based logistic regression classifiers distinguished viable GCT (SEM/N-SEM) from teratoma (Area Under the Curve [AUC] > 0.99) and SEM from N-SEM (AUC = 0.99), outperforming well-known miRNA markers. Target gene analysis implicated FOXO and RUNX1 regulation, somatotroph signaling, and height-related pathways. Overall, our comprehensive tissue-level miRNA profiling in TGCTs identified potential diagnostic biomarkers for histologic subtypes, offering insights into miRNA-mediated transcriptional dysregulation.

overall_design: miRNA-seq of 43 formalin-fixed paraffin-embedded (FFPE) tissue samples from 32 patients (30 primary, 13 metastases) with testicular cancer

first: Anirudh

last: Yerrapragada

first: Stephan

last: Bronimann

first: Carlos

last: Rivera Lopez

first: Joseph

last: Cheaib

first: Yasser

last: Ged

first: Ezra

last: Baraban

first: Shawn

last: Lupold

first: Nirmish

last: Singla


title: Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [ChIP-seq]

first: Yixiang

address: 450 Brookline Ave

institute: Dana-Farber Cancer Institute

summary: Small cell lung cancer (SCLC) is a highly aggressive malignancy that lacks effective targeted therapies, in part due to frequent loss-of-function mutations in tumor suppressors and the absence of recurrent oncogenic drivers. Approximately 15% of SCLCs harbor inactivating mutations in NOTCH1 or NOTCH2, and most neuroendocrine-high SCLCs exhibit low NOTCH activity. Using CRISPR/Cas9 screening in primary cell lines derived from NOTCH1/2-isogenic SCLC genetically engineered mouse models, we identified TRIM28 as a synthetic lethal dependency in NOTCH2-inactivated SCLCs. Loss of TRIM28 in this context robustly induced expression of endogenous retroviruses, activated viral sensing pathways, and triggered a type I interferon response. Mechanistically, NOTCH2 inactivation increased reliance on TRIM28-mediated ERV silencing, creating a hyper-dependence on TRIM28 via the STING–MAVS–TBK1 axis. Notably, TRIM28 was essential for tumor growth only in the setting of NOTCH2 loss. These findings identify TRIM28 as a potential therapeutic target in NOTCH2-deficient or low-NOTCH2-expressing SCLC.

overall_design: 1); ChIP-seq profiling of TRIM28-HA (using HA antibody) in human NCI-H1048 cells (NOTCH2-WT) overexpressing TRIM28-HA. 2); ChIP-seq profiling of TRIM28-HA (using HA antibody) in murine 1014 cells derived from the RPR2 genetically engineered mouse model, with TRIM28-dTAG-HA knock-in and either CRISPR-Cas9–mediated inactivation of NOTCH2 (NOTCH2-inactivated) or a non-targeting control (NOTCH2-WT). 3);ChIP-seq profiling of H3K27ac and H3K9me3 in murine 1014 TRIM28-dTAG-HA NOTCH2-isogenic cells (NOTCH2-WT or NOTCH2-inactivated) treated with 100 nM dTAG-V1 for 72 hours to degrade TRIM28 or with DMSO as a control.

first: Hong

last: Deli

first: Matthew

last: Oser


title: Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [human_bulk_RNA_seq]

overall_design: Bulk RNA-seq profiling of 1) human NCI-H1048 cells with genetic inactivation of NOTCH2 with two independent sgRNAs and non-targeting as a control using CRISPR-Cas9. 2). human NCI-H1048 cells with genetic inactivation of NOTCH2 with an sgRNA or non-targeting control and then genetic inactivation of TRIM28 with an sgRNA or non-targeting control using CRISPR-Cas9.


title: Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [bulk_murine_RNA_seq]

overall_design: Bulk RNA-seq profiling of 1). Neuroendocrine suspension and non-neuroendocrine adherent NOTCH-WT (K93) and NOTCH2-Mutant (K60) SCLC cell lines derived from RPR2 genetically engineered mouse model and genetic inactivation of TRIM28 with two sgRNA and non-targeting control using CRISPR-Cas9.   2). SCLC cell line 1014 cells derived from RPR2 genetically engineered mouse model with TRIM28-dTAG-HA knock-in and genetic inactivation of NOTCH2 with two sgRNA and non-targeting control using CRISPR-Cas9 and treated with 100 nM dTAG-V1 for 72 hours to degrade TRIM28 or with DMSO as a control.


title: Macrophage-derived oncostatin M repairs the lung epithelial barrier during inflammatory damage

first: CBDM

last: Lab

address: 77 Avenue Louis Pasteur

department: Microbiology and Immunobiology

institute: Harvard Medical School

summary: Tissue repair programs must function alongside antiviral immunity to restore the lung epithelial barrier following infection. We found that macrophage-derived oncostatin M (OSM) counteracted the pathological effects of type I interferon (IFN-I) during infection and damage in mice. At baseline, OSM-deficient mice exhibited altered alveolar type II (ATII) epithelial cell states. In response to influenza or viral mimic challenge, mice lacking OSM exhibited heightened IFN-I responses and increased mortality. Furthermore, OSM promoted organoid formation despite the growth-inhibitory effects of IFN-I. These findings identify OSM as an indispensable macrophage-derived growth factor that maintains the homeostasis of lung epithelial cells and promotes their proliferation to overcome IFN-I-mediated immunopathology.

overall_design: To examine the impact of the cytokine Oncostatin M (OSM) on alveolar epithelial phenotype, OSM-sufficient or -deficient mice were intra-tracheally treated with either saline (PBS) or recombinant OSM. RNA was subsequently isolated from FACS sorted  type II alveolar epithelial cells for analysis.

first: Daisy

middle: A

last: Hoagland

first: Patricia

last: Rodríguez-Morales

first: Alexander

middle: O

last: Mann

first: Ruth

last: Franklin


title: Genome-wide gene expression of Yarrowia lipolytica wild-type and mutant(△pex10 harboring DGA1 overexpression plasmid) with or without  1 g/L hexanoic acid

first: Sungmin

last: Hwang

address: Hwarang-ro 14-gil, Seongbuk-gu

department: Clean Energy Research Center

institute: Korea Institute of Science and Technology

summary: The goals of this study are to compare NGS-derived transcriptome profiling (RNA-seq) of Yarrowia lipolytica wild-type and mutant(△pex10 harboring DGA1 overexpression plasmid) upon treatment of mock and 1 g/L hexanoic acid

overall_design: mRNA from biological duplicate or triplicate Yarrowia lipolytica wild-type and mutant(△pex10 harboring DGA1 overexpression plasmid) incubated with or without 1 g/L hexanoic acid

first: Yeon-Ho

last: Choi

first: Sun-Mi

last: Lee


title: Transcriptional programs of cell identity and p53-induced stress responses are associated with distinctive features of spatial genome organization [ChIP-seq]

city: Berkeley

first: Robert

last: Tjian

state: CA

address: University of California, Berkeley 450 Li Ka Shing #3370

department: MCB

institute: UC Berkeley

summary: To date, most studies explored changes in 3D-genome organization between different tissues or during differentiation, which involve massive reprogramming of transcriptional programs. Much fewer studies examined alterations in genome organization in response to cellular stress, which involves less pervasive transcriptional modulation. Here, we examined associations between spatial chromatin organization and gene expression in two different biological contexts: transcriptional programs determining cell identity and transcriptional responses to stress, using p53 activation as a model. We selected 10 cell lines of diverse tissues, and in each performed micro-C, RNA-seq, and p53 ChIP-seq, before and after p53 induction. In the comparison between cell types, we delineated marked correlations between gene expression and spatial genome organization and identified hundreds of active enhancer-promoter loops associated with the expression of cell-type marker genes. In contrast, within each cell type, no such links were observed for expression changes induced by p53 activation, even for enhancers and promoters activated by p53 binding. Our analysis points to a fundamental difference between chromatin interactions that define cell identity and those that are established in response to cellular stress. Our results on p53-induced transcriptional responses support the recently proposed TF activity gradient model, which speculated a contact-independent mechanism for enhancer-promoter communication.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) of p53 transcription factor in 10 cell lines of different tissue of origin in the presence or absence of the p53 activator Nutlin-3a. Input samples are included as control. Two biological replicates for condition.

first: Hsin-Jung

last: Chou

first: Tsung-Han

middle: S

last: Hsieh

first: Claudia

last: Cattoglio

first: Jack

last: Li

first: Xavier

last: Darzacq

first: Gony

last: Shanel

first: Ran

last: Elkon


title: G9a regulated transcriptional programs during B cell differentiation [RNA-seq]

city: Atlanta

first: Chris

last: Scharer

state: GA

address: 1510 Clifton Rd, Suite 3086A

department: Microbiology and Immunology

institute: Emory University

summary: B cell differentiation is tightly regulated through coordinated changes in metabolism, division, expression of transcription factors, and epigenetic programming mediated by histone modifying enzymes.  In this study, we examined the role of an epigenetic writer, the histone H3K9 mono and dimethyltransferse G9a, in regulating the transcriptional programs during B-cell development and plasma cell (PC) formation.  Utilizing a B-cell specific G9afl/flCd19Cre/+ conditional mouse model we performed RNA-seq on naive and activated B cells and plasma cells that formed in response to LPS.

overall_design: Differential RNA expression analysis of RNA-seq data for naïve, activated B and plasma cells from Ctrl and G9a KO samples

first: Christopher

middle: D


title: G9a regulated chromatin accessibility programs during B cell differentiation [ATAC-seq]

summary: B cell differentiation is tightly regulated through coordinated changes in metabolism, division, expression of transcription factors, and epigenetic programming mediated by histone modifying enzymes.  In this study, we examined the role of an epigenetic writer, the histone H3K9 mono and dimethyltransferse G9a, in regulating the chromatin accessibility programs during B-cell development and plasma cell (PC) formation.  Utilizing a B-cell specific G9afl/flCd19Cre/+ conditional mouse model we performed ATAC-seq on naive and activated B cells and plasma cells that formed in response to LPS.

overall_design: Differential chromatin accessibility analysis of ATAC-seq data for naïve, activated B and plasma cells from Ctrl and  G9a KO samples


title: LIGHT in Combination with IL-13 or IL-17 Drives Inflammatory Phenotypes in Human Pulmonary Fibroblasts

city: La Jolla

first: Jeamin

last: Jung

address: 9420 Athena Cir

department: Bioinformatics Core

institute: La Jolla Institute for Immunology

summary: Fibroblasts are primary structural cells involved in tissue remodelling, but recent transcriptomic data have highlighted the ability of fibroblasts to display molecules that contribute to inflammation. Which factors might drive such inflammatory phenotypes are unclear. LIGHT (TNFSF14) is a cytokine that we previously showed was involved in inflammation of the lungs and may be central to lung diseases exhibiting fibrosis and inflammation, including asthma and interstitial lung disease. With RNA-seq, we investigated the activity of LIGHT in human pulmonary fibroblasts compared to IL-13 and IL-17, two other cytokines linked to lung disease. While all three cytokines individually induced both unique and overlapping gene transcripts, when fibroblasts were stimulated with LIGHT and IL-13 they upregulated more inflammatory transcripts including CCL2, CCL26, CXCL2, CXCL3, CXCL5, CXCL6, IL32, CSF2, VCAM1, ICAM1, IL18R1, IL1RL1, TNFRSF12A, TNFRSF4, TNFRSF8, ITGA2, ITGA4, and ITGAV; and when stimulated with LIGHT and IL-17, inflammatory transcripts included CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, IL32, IL33, CSF2, TSLP, IL1A, IL6, IL18, VCAM1, ICAM1, IL18R1, IL1RL1, TNFSF4, TNFRSF4, TNFRSF8, ITGA2, ITGA4, and ITGAV. Furthermore, multiple cell cycle-related transcripts were induced with the combinations of LIGHT with IL-13 or IL-17. Providing physiological significance, some of the fibroblast transcriptional signatures induced by these cytokines were found to be present in subsets of fibroblasts isolated from patients with interstitial lung disease. This study highlights the synergistic activities of LIGHT in lung fibroblasts and suggests it could drive inflammatory activities relevant for several diseases dependent on the availability of other classical cytokines made in the lungs.

overall_design: Bulk RNA seq. analysis from human pulmonary fibroblasts stimulated with 50 ng/ml LIGHT, 25 ng/ml IL-13, and 100 ng/ml IL-17A and in combination of IL13 or Il17A with LIGHT

first: Nandita

last: Ghosh

first: Rinkesh

last: Gupta

first: Kai

last: Fung

first: Michael

last: Croft


title: Transcriptional programs of cell identity and p53-induced stress responses are associated with distinctive features of spatial genome organization [SuperSeries]

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

overall_design: Refer to individual Series


title: Triple therapy reduced metastasis in triple-negative breast cancer

status: Public on Jul 12 2025

city: Shanghai

first: Zhong

last: Yiye

address: No.800 Dongchuan Road

institute: Shanghai Jiao Tong University

summary: Purpose: To understand the underlying mechanisms of oncolytic virus therapy in breast cancer. Methods: The primary tumors of 4T1 in BALB/C mice were extracted and analyzed by RNA-seq. Results: In consistent with previous studies, we found some anti-tumor factors were up-regulated. Interestingly, several immunosupressive genes were activited. Conclusion: Our study identified the intercellular and intercellular factors restricting the optimized oHSV efficacy and supported the rationally designed triple therapy for clinical translation.

overall_design: scRNA-seq was performed in 2 lung samples from BALB/C mice in 2 groups.

first: Zhang

last: Xue

first: Wang

last: Dawei

first: Cai

last: Yujia


title: Transcriptional programs of cell identity and p53-induced stress responses are associated with distinctive features of spatial genome organization [Micro-C]

first: Robert

last: Tjian

overall_design: Micro-C in 10 cell lines of different tissue of origin in the presence or absence of the p53 activator Nutlin-3a. Two biological replicates for condition.

first: Hsin-Jung

last: Chou

first: Tsung-Han


title: Gene community-regulated pathway analysis successfully deciphers pathogenesis and biomarkers of viral versus metabolic hepatocellular carcinoma

city: Hsinchu

first: Jinn-Moon

last: Yang

address: 75 Po-Ai Street

institute: National Chiao Tung University

summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths globally. Understanding its mechanisms is crucial, despite advancements in gene identification. To address the variability of transcriptome data across cohorts and assess the impact of single gene on pathways, we developed a Gene community-Regulated Pathways (GReP) method with an Integrated Gene Community score. Using The Cancer Genome Atlas and the Taiwan Liver Cancer Network cohorts, GReP identified 531 consensus genes and 137 pathways across four categories: central dogma, metabolism, immune, and metastasis. GReP then identified potential biomarkers and categorized patients into metabolic HCC (mostly males with alcoholism and NAFLD) and viral HCC (prone to cirrhosis and HBV/HCV infection) groups, linking genotypes (gene categories) and phenotypes (clinical data) to uncover distinct mechanisms. This approach can be expanded across diverse cohorts to expedite the discovery of promising targets and therapeutic interventions for various diseases.

overall_design: 66 liver samples form heaptocellular carcinoma (HCC) patients and 5 normal liver samples were obtained form the Taiwan Liver Cancer Network (TLCN) for RNA sequencing to identify biomarkers related to HCC.

first: Yu-Hsin

last: Wu

first: Jung-Yu

last: Lee

first: Chih-Yuan

first: Po-Wei

last: Wang


title: FAK regulates trophoblast functions of invasion and proliferation through Rap1 pathway in preeclampsia

city: Chongqing

first: Tingting

address: Youyi road No.1

institute: The First Affiliated Hospital of chongqing Medical University

summary: To explore the potential role of focal adhesion kinase (FAK) in trophoblast functions in early-onset preeclampsia (EOPE).We first examined expression and localization in placental tissue as well as in villus tissue during early pregnancy. Then, FAK activity was inhibited with Y15. The effects of FAK on the invasion and proliferation of trophoblast cells (HTR8/SVneo) were investigated. Transcriptomic and bioinformatics analyses were then used to predict the possible pathways by which FAK is involved in PE. Finally, we measured the expression of FAK in a PE mouse model. Transcriptomic and bioinformatics results suggest that Rap1 may be a downstream regulator of trophoblast FAK. In mouse models, we found reduced expression of FAK and Rap1 in the placenta of PE mice.

overall_design: To further investigate the potential function of FAK in trophoblast cells, we treated the human choriotrophoblast cells HTR-8/SVneo with the specific pY397 autophosphorylation inhibitor Y15, with 3 replicates each in the control and treatment groups.

first: Hai

last: Tong

first: Chen

last: Zhang

first: Xue

first: Hongbo

last: Qi


title: Spinal cord organoids derived from human amniotic fluid iPSC recapitulate the diversity of cell phenotypes during fetal neural tube morphogenesis

first: Shaun

last: Kunisaki

address: 1800 Orleans Street

department: Pediatric Surgery

institute: Johns Hopkins University School of Medicine

summary: We developed spinal cord organoids (SCOs) as an in vitro modeling system to help understand the pathophysiology of the spinal cord in myelomeningocele (MMC). The cell types and development of these SCOs was examined with scRNA sequencing.

overall_design: SCOs were developed from human amniotic fluid induced pluripotent stem cells from both control samples and MMC samples. These SCOs were then characterized with scRNA sequencing.

first: Juan

middle: C

last: Biancotti

first: Hannah

middle: E

last: Moore

first: Anne

last: Sescleifer

first: Shelby

middle: R

last: Sferra

first: Annalise

middle: B

last: Penikis

first: Jena

middle: L

last: Miller


title: Fibronectin-guided immune-stromal cell crosstalk promotes angiogenesis in pulp-dentin complex regeneration

first: Sol

last: Jeong

summary: We discovered the interactions of the macrophages and hDPSC in dental pulp and demonstrated that the effect of fibronectin in dental root regeneration.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for mono-cultured or co-cultured cells

first: So Young

last: Park

first: Do hyun

last: Kim

first: Jin Man


title: scRNA-seq of Mycobacterium tuberculosis-specific CD4 T cells from Kenyan women with and wihtout HIV and before and after ART initiation following stimulation with Mtb WCL

first: Chris

last: Scharer

summary: To understand how HIV and timing of ART initiation affect the transcriptional profile of Mtb-specific CD4 T cells, we performed 10X single-cell RNA sequencing comparing Mtb-specific CD4 T cell transcriptomes from people without HIV, people with HIV prior to ART, and people with HIV after ART from the Mombasa Cohort in Mombasa, Kenya. PBMCs were stimulated overnight with Mycobacterium tuberculosis whole cell lysate and CD40L+CD69+ Mtb-specifc CD4 T cells were sorted for sequencing.

overall_design: scRNA-seq of Mtb-specific CD4 T cells after overnight stimulation with Mycobacterium tuberculosis whole cells lysate

first: Christopher

first: Cheryl

last: Day

first: Rachel

last: Pearson


title: Combined aerobic and resistance exercise training alters the spatial transcriptome of skeletal muscle in young adults

city: Tarrytown

first: Michael

last: Stec

address: 777 Old Saw Mill River Rd

institute: Regeneron Pharmaceuticals

summary: Chronic exercise training substantially improves skeletal muscle function and performance. The repeated demands and stressors of each exercise bout drive coordinated molecular adaptations within multiple cell types in muscle tissue, leading to enhanced neuromuscular recruitment and contractile function, stem cell activation, myofiber hypertrophy, mitochondrial biogenesis, and angiogenesis, among others. To comprehensively profile molecular changes induced by combined resistance and endurance exercise training, we employed spatial transcriptomics coupled with immunofluorescence and computational approaches to resolve effects on myofiber and mononuclear cell populations in human muscle. By computationally identifying fast and slow myofibers using immunofluorescence data of spatially sequenced tissue sections, we identified fiber type-specific, exercise-induced gene expression changes that correlated with muscle functional improvements. Additionally, spatial transcriptome profiling and integration of human muscle single cell RNAseq data identified an exercise-induced shift in interstitial cell populations coincident with angiogenesis. Overall, these data provide a unique spatial molecular profiling resource for exploring muscle adaptations to exercise, and provide a pipeline and rationale for future studies in human muscle.

overall_design: Sendentary and chronic exercise skeletal muscle samples from five health young donors

first: Miachel

middle: J

first: Zachary

last: Graham

first: Qi

last: Su


title: Lentiviral Vectors for Hematopoietic Stem Cell Gene Therapy Restore α-Globin Expression in  α-Thalassemia Red Blood Cells

city: Los Angeles

first: Eva

last: Segura

address: Terasaki Life Sciences Building, Room 3163

department: Department of Microbiology, Immunology & Molecular Genetics

institute: University of California, Los Angeles

summary: Alpha thalassemia major (ATM) is an inherited blood disorder caused by the absence of all four α-globin genes (HBA2/1), resulting in severe anemia and lifelong transfusion dependence. While allogeneic hematopoietic stem cell transplant (HSCT) offers a potential cure, donor availability remains limited. We present a gene therapy approach for autologous HSCT, using lentiviral vectors (LVs) to deliver HBA2 under the regulation of optimized β-globin locus control region (LCR) enhancers, restoring α-globin expression. The best-performing LVs, EV-α and EV-α-UV, achieved 90-100% transduction efficiency in human hematopoietic stem and progenitor cells (HSPCs), optimal vector copy numbers, and a safe integration profile. ATM-derived HSPCs from three donors treated with these LVs yielded α/β-globin mRNA and chain ratios within the therapeutic range (~0.5+), and restored hemoglobin levels by 50 to 100%. These findings establish the safety and clinical potential of EV-α and EV-α-UV as a promising autologous stem cell gene therapy for ATM.

overall_design: Erythroid cells differentiated from bone marrow derived hematopoietic stem and progenitor cells from 2 healthy donors and 1 donor with alpha thalassemia major. Some conditions from the alpha thalassemia major cells were transduced with different alpha globin lentiviral vectors desgined and produced in our laboratory.

first: Kevyn

last: Hart

first: Beatriz

last: Campo Fernandez

first: Devin

last: Brown

first: Kevin

last: Tam

first: Andrea

last: Guiterrez Gracia

last: Seigneurbieux

first: Karen

last: Li

first: Emma

last: Blakely

first: Katelyn

last: Masiuk

first: Roshani

last: Sinha

first: Devesh

last: Sharma

first: John

last: Everett

first: Matthew

last: Hogenauer

first: Kyle

last: Cromer

first: Frederick

last: Bushman

first: Tippi

last: MacKenzie

first: Donald

last: Kohn


title: Molecular mechanism of calcification in vascular smooth muscle cells regulated by Shox2

city: Guangzhou

first: Xiaoyu

last: Liu

address: 253 Industrial Avenue

institute: Zhujiang Hospital, Southern Medical University

summary: Vascular calciﬁcation is one of the most common cardiovascular complications in patients with chronic kidney disease (CKD) and contributes to subsequent cardiovascular mortality. However, the precise mechanisms underpinning vascular calciﬁcation are not fully understood. In the present study, we report the role of Shox2 in vascular calcification. To further explore the molecular mechanism by which Shox2 regulates vascular calcification, we performed high-throughput RNA-seq to identify the target gene of Shox2.

overall_design: Human vascular smooth muscle cells were cultured in growth medium (GM), calcifying medium (CM) and transfected with Ad/GFP or Ad/Shox2. RNA-seq was performed to determine the downstream target of Shox2.

first: Jianyun

last: Yan


title: Lycium barbarum polysaccharide-glycoprotein ameliorates abnormal neural activity in depressive patient-derived ventral forebrain organoids

city: Nanjing

first: Yan

state: Jiangsu

address: 101Longmian Avenue, Jiangning District

department: School of Pharmacy

institute: Nanjing Medical University

summary: Major depressive disorder (MDD) is a severe mood disorder that imposes a significant burden on individuals, families, and society. Despite considerable advances in research, most current treatments for depression remain ineffective for many patients. Given the potential antidepressant properties of Lycium barbarum glycopeptide (LbGp), there is an urgent need to establish a platform for evaluating its therapeutic efficacy and underlying mechanisms. In this study, we generated ventral forebrain organoids derived from MDD patient and observed abnormal neuronal morphology along with impaired calcium dynamics and electrical activity. Treatment with LbGp effectively restored these phenotypic alterations in MDD organoids. Transcriptomic analysis further revealed that LbGp could ameliorate endoplasmic reticulum (ER) stress in MDD organoids. Furthermore, to investigate the role of ER stress, we treated control organoids with the ER stress agonist CCT020312, which induced similar altered neural activity phenotypes that observed in MDD organoids. Remarkably, LbGp treatment rescued the phenotypic defects in control organoids induced by CCT020312. In conclusion, this study utilized ventral forebrain organoids derived from MDD patients and demonstrated that LbGp ameliorates MDD through the modulation of ER stress.

overall_design: Evaluation of the antidepressant potential of Lycium barbarum glycopeptide (LbGp) using human ventral forebrain organoids


title: Correction of splicing defect in compound heterozygous FRDA patient carrying FXN 165+5G>C point mutation.

city: Dallas

first: Marek

last: Napierala

state: TX

address: Marek Napierala

institute: University of Texas Southwestern Medical Center

summary: Friedreich’s ataxia is an autosomal recessive disease caused by mutations in the FXN gene. Approximately 95% of patients harbor homozygous GAA repeat expansion in the intron 1 of the FXN, while the remaining 5% are compound heterozygotes carrying GA expansion on 1 allele and point mutation on the other allele. Here, we characterized a G to C transversion in position 5 of the intron 1 of the FXN. Mutation results in profound downregulation of FXN mRNA and protein levels. Transcriptome and RT-PCR analyses demonstrated aberrant splicing of the FXN gene caused by this mutation that can be at least in part corrected with antisense oligonucleotides (ASOs) targeting intron 1.

overall_design: To define a splicing defect caused by FXN 165=5GtoC mutation in the intron 1 of the frataxin gene we established primary skin fibroblast from Friedreich’s ataxia patient carrying this mutation. After 3 passages total RNA was extracted using Qiagen RNeasy RNA extraction kit and subjected to deep RNA sequencing to identify splicing abnormalities in the FXN locus.

first: Selina

last: Aguilar

first: Pouire

last: Yameogo

first: Jixue

first: David

last: Lynch

first: Jill


title: Expression data from WT and Pik3ca-/- MLLAF9 GMPs (LSCs)

city: Bronx

first: Shira

middle: Gabriella

last: Glushakow-Smith

address: 1300 Morris Park Ave, CH410

institute: Albert Einstein College of Medicine

summary: Acquired non-genetic resistance mechanisms to existing therapies contribute to poor outcomes for acute myeloid leukemia (AML) patients, and inability to target leukemic stem cells (LSCs) can lead to relapse. To overcome these challenges, we tested whether LSCs have dependencies on PI3 kinase.

overall_design: We sorted GFP+ GMPs from the bone marrow of transplant recipient mice and performed DNA microarray analysis on triplicate Pik3ca-/- or five WT samples using the Affymetrix Mouse Transcriptome Assay 1.0 Kit

middle: G

first: Imit

last: Kaur

first: Simone

last: Sidoli

first: Shayda

last: Hemmati

first: Ellen

last: Angeles

first: Taneisha

last: Sinclair

first: Samarpana

last: Chakraborty

first: Aaliyah

last: Battle

first: Kristina

last: Ames

first: Swathi-Rao

last: Narayangari

first: Ulrich

last: Steidl

first: Aditi

last: Shastri

first: Amit

last: Verma

first: Kira

last: Gritsman

first: Rotila

last: Hyka

first: Mark

last: Soto

first: Melissa

last: Tracy

first: Jayaram

last: Vankudoth

first: Seiya

last: Kitamura

first: Linde

last: Miles


title: Transcriptional programs of cell identity and p53-induced stress responses are associated with distinctive features of spatial genome organization [RNA-seq]

first: Robert

last: Tjian

summary: To date, most studies explored changes in 3D-genome organization between different tissues or during differentiation, which involve massive reprogramming of transcriptional programs. Much fewer studies examined alterations in genome organization in response to cellular stress, which involves less pervasive transcriptional modulation. Here, we examined associations between spatial chromatin organization and gene expression in two different biological contexts: transcriptional programs determining cell identity and transcriptional responses to stress, using p53 activation as a model. We selected 10 cell lines of diverse tissues, and in each performed micro-C, RNA-seq, and p53 ChIP-seq, before and after p53 induction. In the comparison between cell types, we delineated marked correlations between gene expression and spatial genome organization and identified hundreds of active enhancer–promoter loops associated with the expression of cell-type marker genes. In contrast, within each cell type, no such links were observed for expression changes induced by p53 activation, even for enhancers and promoters activated by p53 binding. Our analysis points to a fundamental difference between chromatin interactions that define cell identity and those that are established in response to cellular stress. Our results on p53-induced transcriptional responses support the recently proposed TF activity gradient model, which speculated a contact-independent mechanism for enhancer–promoter communication.

overall_design: Gene expression profiling (RNA-seq after rRNA depletion) of 10 cell lines of different tissue of origin in the presence or absence of the p53 activator Nutlin-3a. Two biological replicates for condition.

first: Hsin-Jung

last: Chou

first: Tsung-Han

last: Hsieh

first: Claudia

last: Cattoglio

first: Jack

last: Li

first: Xavier

last: Darzacq

first: Gony

last: Shanel

first: Ran

last: Elkon


title: Study of Molecular and Transcriptomic Age-related Changes in the Dorsal and Ventral Areas of Hippocampus in the 5xFAD Mouse Model of Alzheimer’s Disease

status: Public on Jul 09 2025

city: Moscow

first: Vasiliy

last: Akimov

email: VAkimov@cspfmba.ru, vasoakim@gmail.com

address: Pogodinskaya Street, 10, bld. 1

institute: Centre for Strategic Planning of FMBA of Russia

summary: We performed snRNA-seq of 8, 16 and 22 month old mice of 5xFAD (B6SJL/Tg) line together with control B6SJL mice to assess the changes which occur due to progression of Alzheimer's disease.

overall_design: Tissues of the dorsal and ventral parts of the hippocampi from 16 male animals of 8, 16 and 22 month old, respectively, were isolated to perform snRNA-seq.

first: S

last: Shkil

first: P

last: Fortygina

first: O

last: Antonova

first: N

last: Bugaev-Makarovskiy

first: V

last: Fateev

first: A

last: Borodinova

last: Yudin

last: Makhotenko

last: Keskinov

first: E

last: Snigir

last: Gancharova

last: Balaban

first: D

middle: V

last: Svetlichnyy

middle: I

last: Skvortsova


title: XMD8-92 and JWG-045 exhibit anti-ferroptotic activities, independently of inhibiting ERK5

city: Manchester

first: Cathy

last: Tournier

address: Dover Street

department: Division of Cancer Sciences

institute: The University of Manchester

summary: Extracellular-regulated protein kinase 5 (ERK5) is a promising target in cancer therapy, and several ERK5 inhibitors have been developed. In this study, we observed that the inhibitors XMD8-92 and JWG-045 exhibited  n anti-ferroptotic activity in breast cancer cells, which was not detected with two other ERK5 inhibitors JWG-071, BAY-885, or the MEK5 inhibitor BIX02189. Using CRISPR-mediated gene editing, we generated ERK5- eficient breast cancer cells and found that XMD8-92 and JWG-045 protected these cells from ferroptosis, indicating clear off-target effects of these inhibitors. RNA sequencing revealed that XMD8-92 might influence  erroptosis through the regulation of the oxidative stress-related genes KEAP1 and GCH1. Collectively, these results demonstrate that XMD8-92 and JWG-045 can act independently of ERK5 inhibition, underscoring the  mportance of using more specific inhibitors, such as JWG-071, BAY-885, or BIX02189, to evaluate the role of ERK5 signalling in cancer. Furthermore, our data emphasise the critical need for combining bioinformatics  nd experimental validation to correctly assign functional roles to specific proteins in biological processes.

overall_design: BT474 cells were treated with 5 μM XMD8-92, an ERK5 inhibitor, for 0, 2, 4, and 6 hours. For each time point, three biological replicates were collected, resulting in 12 samples. Additionally, DMSO-treated control samples (one replicate each) were included for the 2-, 4-, and 6-hour time points, bringing the total number of samples to 15.

first: Wei

last: Zhang

first: Adam

last: Pearson


title: Epigenetic regulation of B cell differentiation by G9a

first: Chris

last: Scharer

overall_design: Refer to individual Series


title: Studies on the mechanisms underlying human epidermal stem cell differentiation by epigallocatechin gallate

city: Suzhou

first: Rui

middle: xing

last: Hou

address: No.5, Tayun Road, Wuzhong District

department: Key Laboratory of Hand Surgery

institute: Suzhou Ruihua Orthopedic Hospital

summary: To elucidate the mechanism by which epigallocatechin gallate (EGCG) promotes the differentiation of epidermal stem cells (EpSCs), we performed RNA sequencing (RNA-seq) on EpSCs treated with or without 2 μM EGCG for 3 days. This analysis revealed the transcriptome profile regulated by EGCG.

overall_design: EpSCs were isolated from human skin, cultured, and treated with or without 2 μM EGCG. RNA was isolated from the cells for RNA sequencing.

first: Ruixing

first: Zuohua

last: Liu


title: mTORC1 hyperactivation blocks pluripotent stem cells fate transitions through TFE3-NuRD association

first: shuhui

last: xu

address: 190 Kaiyuan Avenue, Huangpu District

institute: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

summary: As an evolutionarily conserved master regulator of metabolism, mechanistic target of rapamycin complex 1 (mTORC1) regulates cell states and fates in development, cancer and aging. mTORC1 activity regulation was critical for pluripotent stem cells maintenance and cell fate transitions. Inhibition of mTORC1 induces embryonic stem cells (ESCs) entry into a paused state which reversibly arrests self-renewal leaving pluripotency intact. Hyperactivation of mTORC1 impedes both pluripotency re-establishment and exit of PSCs. As shown that mTORC1 mediates TFE3 nuclear translocation block pluripotency exit, whether similar mechanisms through transcription factor TFE3 are involved in these processes, and the detailed mechanism by which mTORC1-TFE3 regulates critical transcriptional processes for these transitions, remain unclear. In this study, we demonstrate that the nuclear translocation of TFE3, induced by hyperactivation of mTORC1, results in its binding to the nucleosome remodeling and deacetylation (NuRD) complex in both re-establishment and exit of pluripotency. This interaction inhibits the expression of various crucial genes during different fate transitions of PSCs. Our findings uncover a common and key role of TFE3-NuRD association as mediator of mTORC1 to block pluripotent cell fate transitions, with implications for various fields including physiological and pathological diseases.

overall_design: This submission contains two parts, The first part includes CUT&TAG profiles of TFE3 and RBBP4 in OSKM-induced reprogramming (D12) iPSCs under three conditions: wild-type (WT), Tsc1 knockout (KO), and Tsc1 KO with Rapamycin (0.3nM) treatment; and the second part CUT&Tag sequencing data from mouse embryonic stem cells (mESCs) under different culture conditions and genetic backgrounds. The dataset includes eight samples representing: (1) wild-type , (2) Tsc1 knockout (Tsc1 KO), and (3) Tsc1 KO with rapamycin treatment (0.3nM) mESCs cultured in either 2iL (pluripotency-maintaining) or N2B27 (differentiation, 40h) conditions. For each sample group, chromatin profiling was performed using antibodies targeting the transcription factor TFE3 and the NuRD complex subunit RBBP4.

first: Peizhi

last: Li

first: Xueting

last: Xu

first: BaoMing

last: Qin

first: Shuhui


title: In vivo CRISPR Screening Identifying Therapeutic Target to Sensitize Anti-PD-1 Immunotherapy in Non-small Cell Lung Cancer

first: Minlin

last: Jiang

address: SiPing Road NO.1239

institute: Tongji University

summary: Although immunotherapy has achieved great success in lung adenocarcinoma (LUAD), only a subset of patients exhibit a favorable response. Leveraging LUAD mono-immunotherapy RNA-sequencing data, we identified differentially expressed genes associated with immunotherapy efficacy by comparing immunotherapy-sensitive and immunotherapy-insensitive patients. These genes were utilized to construct a customized sgRNA library. Two in vivo CRISPR screening models including Lewis lung carcinoma (LLC) and KrasG12D/Trp53-/-(KP) models were developed to identify novel targets regulating immunotherapy efficacy. After transducing the customized sgRNA library, LLC/KP-Cas9 library cells were injected into mice divided into three groups: Rag1-/- C57BL/6 immunodeficient mice treated with IgG antibody, and wild type C57BL/6 immunocompetent mice treated with anti-PD-1 antibody or isotype IgG antibody. Tumors were harvested after 2-4 weeks of treatment, genomic DNA was isolated, and next-generation sequencing (NGS) was performed to analyze sgRNA distribution. By comparing the sgRNAs detected in wild-type C57BL/6 immunocompetent mice treated with anti-PD-1 antibody versus isotype IgG, potential targets that regulating immunotherapy efficacy were identified.

overall_design: Lewis lung carcinoma and KrasG12D/Trp53-/- mouse models were used for in-vivo CRISPR screen. The mice were divided into 3 groups randomly, including Rag1-/- C57BL/6 immunodificient mice with IgG antibody treatment, wild type C57BL/6 immunocompetent mice with treatment of anti-PD-1 antibody or isotype IgG antibody.

first: Congli

last: Hu

first: Jiawei

last: Dai

first: Haowei

last: Wang

first: Hui

last: Lu

first: Guanghui

last: Gao

first: Xuefei

first: Lei

last: Cheng

first: Chao

last: Zhao

first: Yunhuan

first: Fei

last: Zhou

first: Caicun


title: RtmR is a membrane-embedded RRM-family RNA-binding protein that regulates biofilm formation

city: Madison

first: Jacob

middle: Alan

last: Vander Griend

state: Wisconsin

address: 1550 Linden Drive

department: Medical Microbiology and Immunology

institute: University of Wisconsin - Madison

summary: The animal symbiont Vibrio fischeri has served as a model organism for molecular processes underlying bacterial group behaviors, including quorum sensing and biofilm development. Here, using a genetic approach to identify negative regulators of biofilm formation in V. fischeri, we identified a membrane-bound RNA-binding protein, RtmR (VF_2432), that acts as an inhibitor of the symbiosis polysaccharide (SYP) biofilm. Membrane localization of the protein seems to be required for protein stability, as truncation of the transmembrane helices led to an inability to detect the protein. The conserved RNP1 and RNP2 motifs in RtmR’s cytoplasmic RNA recognition motif (RRM) domain are required for function, and we demonstrate binding to RNA substrates. Identification of RtmR RNA ligands was conducted with a CLIP-seq approach that revealed a large interactome. One transcript identified was that of the biofilm regulatory histidine kinase RscS. We found that RtmR biofilm inhibition depends on RscS activity and that RtmR negatively regulates levels of RscS. Overall, this work characterizes a novel type of bacterial RNA-binding protein.

overall_design: iCLIP-Seq (Lee et al. 2021) was conducted with Vibrio fischeri carrying a 3XFLAG tagged allele of gene product VF_2432 (RtmR). Two biological replicates were conducted.

first: Hunter

last: Nottage

first: Andrew

last: Mehle

first: Mark

last: Mandel


title: Single cell RNA sequencing for longitudinal human peripheral blood from HR+ breast cancer patients treated with immunotherapy

city: Nashville

first: Justin

last: Balko

state: TN

address: 658 Preston Research Building

institute: Vanderbilt University

summary: The limited benefit of immune checkpoint inhibitor in breast cancer indicates the pressing need to identify biomarkers of response to minimize risk and maximize benefit. In this study, we performed single cell RNA sequencing and T cell receptor sequencing on peripheral blood mononuclear cells to monitor the peripheral immune dynamics of an exploratory cohort of hormone receptor positive breast cancer patients treated with neoadjuvant nab-paclitaxel+pembrolizumab with the ultimate goal of identifying potential peripheral blood predictive biomarkers.

overall_design: CITEseq+TCRseq: single cell RNA and TCR sequencing was performed on longitudinal peripheral blood immune cells collected from HR+ breast cancer patients treated with immune checkpoint inhibitors.Samples (targeting 15,000 cells/sample for processing and 10,000 cells/sample for sequencing) will be processed for single cell 5' RNA, V(D)J, and Feature Barcode sequencing utilizing the 10X Chromium system. Sequencing will be performed on the Illumina NovaSeq 6000 targeting 50,000 reads per cell for the 5 assay and 5,000 reads per cell for the V(D)J and Feature Barcode assays.

first: Xiaopeng

last: Sun

first: Margaret

last: axelrod


title: Hematopoietic loss of Y chromosome activates immune checkpoints to impair senescent cell clearance contributing to renal disease

city: Charlottesville

first: Nicholas

middle: W

last: Chavkin

address: 415 Lane Road

institute: University of Virginia

summary: The accumulation of senescent cells contributes to morbidity and mortality; however, common mechanisms underpinning this age-associated phenomenon remain elusive. Notably, hematopoietic loss of the Y chromosome (LOY) is the most frequently acquired somatic mutation in males, and this condition has been associated with various age-associated diseases and reduced lifespan. Therefore, we investigated the role of hematopoietic LOY in promoting cellular senescence, focusing on kidney disease due to its well-documented connection with aging and senescence. Herein, a prospective cohort study revealed that LOY in blood is associated with an increased incidence of kidney diseases. Analyses of transcriptional signatures in human kidneys found that immune cell LOY is enriched in patients with kidney disease and associated with greater levels of cellular senescence. In mice, hematopoietic LOY led to renal dysfunction that was accompanied by senescent cell accumulation in models of kidney injury and advanced age. Accordingly, treatment with a senolytic agent promoted senolysis and preferentially inhibited the progression of renal dysfunction in LOY mice. The hematopoietic LOY condition led to the upregulation of multiple immune inhibitory receptors. Treatment with the combination of antibodies targeting PD-1 and SIRP reduced senescent cell accumulation and rescued the renal pathology conferred by hematopoietic LOY. These data indicate that hematopoietic LOY contributes to pathologic conditions by impairing the clearance of senescent cells through upregulation of immune checkpoint proteins.

overall_design: Kidney tissue was isolated from aged mice undergoing bone marrow transplantation to generate hematopoietic Control or LOY conditions, some of which were treated with Conrtol or Senolytic ABT-263 compound. Total RNA was purified, prepped for RNA sequencing, and sequenced. Raw sequencing output was aligned.

first: Yohei

last: Arai

first: Kenneth

last: Walsh


title: FAM72A promotes UNG2 degradation and mutagenesis in human cancer cells

city: Toronto

first: Yuqing

last: Feng

state: ONTARIO

address: 4700 Keele Street

country: Canada

institute: York University

summary: Genetic lesions drive cancer development and progression, and understanding their origins will reveal the mechanisms of carcinogenesis. We showed that murine FAM72A promotes mutagenic DNA repair during antibody maturation by acting as a substrate adaptor of the CTLHMKLN1 E3 ligase to induce the proteasome degradation of Uracil DNA glycosylase 2 (UNG2), a pivotal enzyme of the base excision repair. In humans, the FAM72 gene has expanded to include four paralogues named FAM72A-D. Bioinformatic studies suggested that the human FAM72 genes are overexpressed in a broad range of cancers. However, the functional roles of FAM72A-D in human biology and cancer are unknown. Here, we show that FAM72 family members are minimally expressed in most healthy tissues except for thymus, and that FAM72A, B and D are overexpressed in primary tumorigenic tissues. Human FAM72 expression inversely correlates with UNG2 protein level in human cell lines and primary tumorigenic tissues suggesting that human FAM72 promotes UNG2 degradation. However, only FAM72A is able to bind to and induce UNG2 degradation in human cells. Our results suggest that the ability of FAM72A to induce UNG2 degradation contributes to neoplasia in a variety of cancer types by promoting mutagenic repair of genomic dUs.

overall_design: RNA-seq profiling of 6 human cell lines

first: Philip

last: Barbulescu

first: Chetan

last: Chana

first: Melika

last: Shirdarreh

first: Hong

last: Yang

first: Lizhen

last: Wu

first: Sami

last: Mamand

first: Mohammad

last: Kashem

first: Zia

last: Amin

first: Ming

last: Han

first: Julissa

last: Tsao

first: Trevor

last: Pugh

first: David

last: Cescon

last: Schatz

first: Frank

last: Sicheri

first: Alberto

last: Martin

first: Rossanna

last: Pezo


title: Gene expression of pediatric germ cell tumors using NanoString PanCancer Immune Profiling Panel

city: Barretos

first: LENILSON

last: SILVA

state: SP

address: Rua Antenor Duarte Viléla, 1331

department: Molecular oncology research center

country: Brazil

institute: Barretos Cancer Hospital

summary: The present study aimed to explore the immune landscape of pediatric germ cell tumors to  uncover subtype-specific immunological features and identify potential  immunotherapeutic targets.

overall_design: We included 21 formalin-fixed paraffin-embedded (FFPE) samples obtained from pediatric patients diagnosed with germ cell tumors (GCTs) at Barretos Cancer Hospital, São Paulo, Brazil. The cohort comprised 17 tumor samples: disgerminoma (n=6), yolk sac tumor (n=5), embryonal carcinoma (n=3), and mixed central nervous system tumors (n=3), as well as four non-tumoral samples derived from adjacent normal tissues (two ovarian and two testicular). All tumors were chemo-naïve and reviewed by an experienced pediatric pathologist.  Gene expression assays were performed in the nCounter® FLEX Analysis System, using the PanCancer Immune Profiling Panel (NanoString Technologies, Inc., Seattle, WA).

first: Lenilson

last: Silva

first: Ingridy

last: Cardoso

first: Marcelo

last: da Cruz

first: Thaíssa

middle: M

last: Faria

first: Gisele

last: Martins

first: Bruna

last: Mançano

first: Luiz

middle: F

last: Lopes

first: Rui

last: Reis

first: Daniel

middle: A

last: Moreno

first: Mariana

middle: T

last: Pinto


title: The small but versatile DSS1 protein is required for proper Integrator–PP2A function [ChIP-seq]

city: Shanghai

first: Aixia

last: Song

address: Dong'an Road

institute: Fudan University

summary: Integrator-PP2A (INTAC) is a highly modular complex orchestrating the transition of paused RNA polymerase II into productive elongation or promoter-proximal premature termination, with its loss resulting in transcription dysregulation and genome instability. Here, we identify human DSS1—a flexible 70-residue protein found in multiple functionally diverse complexes including the 26S proteasome—as an integral subunit of the INTAC backbone. Structural analysis of DSS1–INTAC, both alone and in association with paused polymerase, demonstrates intimate interactions between DSS1 and the INTAC backbone. We identify tryptophan 39 of DSS1 as being critical for interacting with INTAC and find that its mutation disrupts DSS1’s interaction with INTAC, while maintaining DSS1’s interaction with the proteasome. This substitution not only impairs INTAC-dependent transcriptional regulation, but also reveals that INTAC is DSS1’s major chromatin-bound form. Together, our findings reveal a role for the versatile DSS1 protein in supporting the structure and regulatory functions of INTAC.

overall_design: CUTTag for DSS1 (Flag-tagged) and Chromatin Immunoprecipitation (ChIP)-seq of Pol II NTD and INTAC complex in DLD1 cell line

first: Congling

last: Xu

first: Qianxing

last: Zhou

first: Fei

middle: X

last: Chen


title: The small but versatile DSS1 protein is required for proper Integrator–PP2A function [CUT&Tag]


title: IL-1 Signaling Blockade in Human Lymphocytic Myocarditis

city: Saint Louis

first: Pan

last: Ma

state: United States

address: CSRB, Room 9918, 425 S Euclid, Saint Louis, MO, 63110

institute: Washington University in Saint Louis

summary: Lymphocytic myocarditis is characterized by infiltration of lymphocytes and macrophages. Current treatment for lymphocytic myocarditis is limited to corticosteroids and a proportion of patients progress to require heart transplantation or durable mechanical circulatory support within a year. Increasing attention is directed toward targeting pro-inflammatory mediators in myocarditis. One promising candidate is IL-1. Here, we investigated a patient with underlying autoimmune disease and biopsy confirmed lymphocytic myocarditis who was initially treated with corticosteroids and experienced clinical deterioration requiring temporary mechanical circulatory support. Rilonacept was consequently administered as a salvage therapy. Pathologically, rilonacept reduced inflammation and fibrosis. We performed spatial transcriptomics (ST) on formalin-fixed paraffin-embedded endomyocardial biopsy samples to further investigate how the cardiac immune landscape is modulated by rilonacept.

first: Jesus

last: Jimenez

first: Ana

last: Villanueva

first: Guanhua

last: Wu

first: Diane

last: Bender

first: Melisa

last: Hector-Greene

first: Chieh-Yu

last: Lin

first: Kory

last: Lavine


title: ATAC-seq(Assay of Transposase Accessible Chromatin with High-throughput sequencing) after ER stress

city: Hefei

first: Yue

last: Zhu

address: The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

summary: Endoplasmic reticulum stress was induced by tunicamycin in hepatocellular carcinoma cells, and chromatin opening detection was performed to search for different chromatin opening sites and different target genes, and then to find the different motif.

overall_design: We performed ATAC-seq to understand the different chromatin opening sites in ER-stressd HCC cells. After obtaining Peaks, perform Peaks annotation to find peak belonging genes, and perform structural statistics for peak affiliated genes.

first: Guoping

last: Sun

first: Jiatao

last: Liu


title: Modulating Immune-Stem Cell Crosstalk Enables Robust Bone Regeneration via Tuning Compositions of Macroporous Scaffolds

city: Lexington

first: Ni

last: Su

state: KY

address: 760 PRESS AVE

institute: University of Kentucky

summary: Cellular crosstalk is critical for tissue healing. Following bone injury, macrophages (Mφ) initiate the immune response by secreting signals that recruit mesenchymal stem cells (MSC) and other niche cells to shape healing. Despite its importance, most studies focus on designing biomaterials that modulate individual cell type, leaving the potential of enhancing bone regeneration by modulating immune-stem cell crosstalk largely unexplored. Here, we report a macroporous microribbon (µRB) scaffold with tunable ratios of gelatin (Gel) and chondroitin sulfate (CS), achieving rapid endogenous bone regeneration in a critical-sized defect model without exogenous growth factors or cells. The 3D MSC/Mφ co-culture model, but not the mono-culture model, effectively identified Gel50_CS50 as the leading ratio for accelerating bone regeneration in vivo. Single-cell sequencing (scRNAseq) of cells infiltrated at day 7 showed Gel50_CS50 led to distinct cellular compositions changes compared to Gel100, and identified a unique M2-like 2 Mφ subpopulation associated with robust bone regeneration. CellChat analysis revealed that Gel50_CS50 significantly enhanced the frequency and intensity of cellular crosstalk among Mφ and other bone niche cell types, with signaling pathways linked to immunomodulation, angiogenesis, and osteogenesis. This study demonstrates Gel50_CS50 µRB as a promising biomaterials-based therapy for treating critical-sized bone defects by modulating cellular crosstalk.

overall_design: Cranial bone defect tissue samples were harvested at week 1 from mice treated with Gel100 and Gel50_CS50, with five mice per material composition. Single cell suspensions were prepared from harvested scaffolds and analyzed using scRNA-seq.

first: Heena

last: Saqib

first: Cassandra

last: Villicana

first: Sungwon

last: Kim

first: Thomas

middle: H

last: Ambrosi

first: Peyton

last: Freeman

first: Tayne

first: Xingming

last: Tong

first: Manish

last: Ayushman

first: Charles

last: Chan

first: Fan

last: Yang


title: GPR146 facilitates blood pressure elevation and vascular remodeling via PIEZO1

city: Beijing

first: Jun

last: Cai

state: --- Select One ---

institute: Fuwai Hospital

summary: RNA seq data of human aortic smooth muscle cell (HASMC) under 100- or 200-mmHg treatment

overall_design: human aortic smooth muscle cell (HASMC) under 100- or 200-mmHg treatment (n=3)


title: Bidirectional feedforward regulatory loop of Dicer-like 4 and flavonoids causes floral bicolor patterning in petunia and dahlia

city: Kusatsu, Shiga

first: Midori

last: Tabara

address: 1-1-1, Noji-Higashi

institute: Ritsumeikan University

summary: Floral bicolor pigmentation is caused by naturally occurring RNA interference (RNAi) in some cultivars of petunia and dahlia. In both plants, the chalcone synthase gene is highly expressed only in the pigmented region of bicolor petals. However, it remains unknown why RNAi is induced only in the unpigmented region. To elucidate the mechanism of this bicolor pattern formation, we examined the dicing activity of Dicer-like 4 (DCL4), which produces small interfering RNAs essential for RNAi. We showed that the crude extract in the pigmented region inhibits DCL4 activity, but not when flavonoids were depleted from the extract. Moreover, we showed the inhibitory activity was associated with flavonoid aglycons. The in vivo dicing activities were detected in the intact protoplasts prepared from the unpigmented region but not from the pigmented region. These results suggest that in the unpigmented region, flavonoids that inhibit DCL4 are not synthesized, and RNAi is maintained, whereas in the pigmented region, DCL4 (RNAi) is inhibited by flavonoids and anthocyanin biosynthesis is maintained. The results of small RNA-seq analyses of bicolor petals and exogenous flavonoid application experiments support this conclusion. Therefore, a clear bicolor pattern is generated by the bidirectional feedforward mechanism of antagonizing DCL4 and flavonoids.

overall_design: To investigate whether Flavonoid compounds inhibit whole 21-nt siRNA producing activity of DCL4, we extracted RNA from red and white region of bicolor petal.

first: Kuriyama

last: Kazunori

first: Ohno

last: Sho

first: Tabara

last: Midori

first: Yaazaki

last: Niichi

first: Koiwa

last: Hisashi

first: Moriyama

last: Hiromitsu

first: Fukuhara

last: Toshiyuki


title: Epigenetic priming of neural progenitors by Notch enhances Sonic hedgehog signaling and establishes gliogenic competence [RNAseq_e17]

city: Aurora

first: Santos

last: Franco

state: CO

department: Pediatrics

institute: University of Colorado Anschutz Medical Campus

summary: The remarkable cell diversity of multicellular organisms relies on the ability of multipotent progenitor cells to generate distinct cell types at the right times and locations during embryogenesis. A key question is how progenitors establish competence to respond to the different environmental signals required to produce specific cell types at critical developmental timepoints. We addressed this in the mouse developing forebrain, where neural progenitor cells must switch from producing neurons to making oligodendrocytes in response to increased Sonic Hedgehog (SHH) signaling during late embryogenesis. We show that progenitor responses to SHH are regulated by Notch signaling, thus permitting proper timing of the neuron-oligodendrocyte switch. Notch activity epigenetically primes genes associated with the oligodendrocyte lineage and SHH pathway, enabling amplified transcriptional responses to endogenous SHH and robust oligodendrogenesis. These results reveal a critical role for Notch in facilitating progenitor competence states and influencing cell fate transitions at the epigenetic level.

overall_design: RNA-seq profiling of Emx1-cre; LSL-NICD and Emx1-cre control dorsal forebrain progenitors at E17.5

first: Luuli

middle: N

last: Tran

first: Ashwini

last: Shinde

first: Kristen

last: Schuster

first: Aiman

last: Sabaawy

first: Emily

last: Dale

first: Madalynn

last: Welch

first: Trevor

last: Isner

first: Sylvia

last: Nunez

first: Fernando

last: García-Moreno

last: Sagerström

first: Bruce

last: Appel


title: Epigenetic priming of neural progenitors by Notch enhances Sonic hedgehog signaling and establishes gliogenic competence [ATACseq_e16]

overall_design: ATAC-seq profiling of Emx1-cre; LSL-NICD and Emx1-cre control dorsal forebrain progenitors at E16.5

first: Charles


title: Epigenetic priming of neural progenitors by Notch enhances Sonic hedgehog signaling and establishes gliogenic competence [RNAseq_e16]

overall_design: RNA-seq profiling of Emx1-cre; LSL-NICD and Emx1-cre control dorsal forebrain progenitors at E16.5


title: A population of  Regulatory T cells controls nociception through enkephalins to restrain skin inflammation.

city: La Jolla

first: Stanislav

last: Dikiy

address: 10550 North Torrey Pines Road

institute: Scripps Research

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

overall_design: Refer to individual Series