title: Overexpressed PRR11-SKA2-miR301a/454 bidirectional transcription unit essentially and coordinately promotes PI3K-AKT pathway activation and lung cancer progression

city: Chongqing

first: youquan

last: bu

address: Medical College Road No.1

institute: Chongqing Medical University

summary: Gene pairing is a highly conserved and special mode of eukaryotic gene organization, and critically implicated in development and diseases including cancer. We previously found that PRR11 and SKA2 constitute a classic head-to-head gene pair. Here, we further demonstrate that PRR11, SKA2, and its intronic miR301a and miR454 constitute a more exquisite bidirectional transcription unit that are overexpressed in various types of cancers. Functional studies using lung cancer as a model system reveal that co-overexpression of PRR11, SKA2, miR301a and miR454 together remarkably accelerates cell growth, cell cycle progression and cell motility in lung cancer cells, and promotes tumor growth in mouse models in vivo, whereas CRISPRi-mediated repression of the entire transcription unit inhibits these malignant phenotypes. Mechanistically, the four component genes do not display any additive or synergistic effect, but rather compensate for each other for robustly sustained activation of PI3K-AKT pathway, with PRR11 interacting with GRB2, and SKA2 with EGFR. Notably, miR301a and miR454 exert their oncogenic functions at least partially via repressing PTEN translation. Moreover, the transcription unit presents as a prominent prognostic meta-marker for lung cancer. Collectively, these findings demonstrate the essential and coordinated roles of PRR11-SKA2-miR301a/454 bidirectional transcription unit in lung cancer progression, highlighting its potential diagnostic and therapeutic values in cancers.

overall_design:
To investigate the molecular mechanisms by which the PRR11/SKA2/miR301a/miR454 transcriptional unit promotes lung cancer development, we conducted four sets of experiments in A549 cells. In the first set, we established stable cell lines with suppressed bidirectional promoter transcriptional activity of PRR11/SKA2 using the CRISPRi system. In the second set, we established stable cell lines with individual overexpression of PRR11, SKA2, as well as co-overexpression of PRR11 and SKA2, using the Lenti-pCDH-CMV system. In the third set, we established stable cell lines with individual overexpression of miR301a, miR454, as well as co-overexpression of miR301a and miR454, using the Lenti-pCDH-CMV system. In the fourth set, we established cell lines with knockout of pre-miR301a and pre-miR454, respectively, using the CRISPRd system.
We subsequently conducted gene expression profiling analysis using RNA-seq data obtained from these four experimental groups.
Comparative gene expression profiling analysis was conducted on the RNA-seq data. For the first group, we compared the stable cell lines with suppressed bidirectional promoter transcriptional activity of PRR11/SKA2 (CRISPRi_PRR11+SKA2 promoter-sgRNA#1) with their corresponding control cell lines (CRISPRi_Mock sgRNA). In the second group, we compared the stable cell lines with individual overexpression of PRR11, SKA2, and co-overexpression of PRR11 and SKA2 (LV-PRR11, LV-SKA2, LV-P+S) with their respective control cell lines (LV-vector-PS). For the third group, we compared the stable cell lines with individual overexpression of miR301a, miR454, and co-overexpression of miR301a and miR454 (LV-miR301a, LV-miR454, LV-3+4) with their corresponding control cell lines (LV-vector-34). Lastly, for the fourth group, we compared the cell lines with knockout of pre-miR301a and pre-miR454 (CRISPRd_miR301a-#2, CRISPRd_miR454-#1) with their respective control cell lines (CRISPRd_Control).

first: Tao

first: Xiaofeng

last: Zuo

first: Shijie

last: Sun

first: Kailong

last: Du


title: HIV-1 transcription dominates over host gene activity at the HIV-1 integration site [ATAC-seq]

status: Public on Oct 21 2025

city: New Haven

first: Ya-Chi

last: Ho

state: CT

address: 295 Congress Ave

country: USA

institute: Yale University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Despite effective antiretroviral therapy (ART), HIV-1 persists as an integrated DNA provirus in the genome of infected cells. Host cells can regulate HIV-1 transcription at the HIV-1 integration site dependent on the location (actively transcribed genes vs repressive chromatin) and the orientation (in the same vs opposite orientation of the host gene transcription) of HIV-1 integration. Presumably, HIV-1 follows the host gene transcriptional activity at the HIV-1 integration site. We interrogated HIV-1-host gene transcriptional interactions at the HIV-1 integration site using CRISPR-mediated activation and inhibition of the host genes (in which HIV-1 was integrated) in seven HIV-1-infected Jurkat T cell clones with known HIV-1 integration sites in the introns of actively transcribed genes and a non-genic region. Using ATAC-seq and strand-specific RNA-seq to examine chromatin accessibility and RNA transcription levels, we found that host gene activation did not increase HIV-1 transcription, while host gene inhibition did not decrease HIV-1 transcription. HIV-1 drove high levels of aberrant host RNA transcription regardless of the HIV-1 integration orientation. HIV-1-driven aberrant host RNA transcription was inhibited by CRISPR-mediated HIV-1 inhibition but not by CRISPR-mediated host gene activation or inhibition. When HIV-1 was integrated into a non-genic region, HIV-1 increased host chromatin accessibility and drove high levels of aberrant host RNA transcription. Overall, HIV-1 LTR promoter-driven transcriptional activity dominated over the host promoter activity. HIV-1 transcription does not passively follow host gene activity. Our results highlight that despite effective ART, silencing HIV-1 promoter is required to inhibit HIV-1-driven aberrant host gene expression and chronic immune activation.

overall_design: Triplicate ATAC-seq profiling of Jurkat T cells infected with a single copy of replication-defective HIV-GFP, transduced with CRISPRa (dCas9-VP64 and MS2-P65-HSF1 transcription activator) or CRISPRi (dCas9-KRAB). Cell lines contain either nontargeting gRNA, HIV-targeting gRNA, or gRNA targeting the host gene containing the HIV integration site. Genomic DNA was prepared via ATAC-seq protocol and isolated by Qiagen MinElute PCR cleanup kit, (#28004) and library prep performed with NEBNext Ultra II Q5 master mix (NEB #M0544X) and Nextera indexed according to NEBNext Ultra II (NEB #E7645). Following baseline amplification, typically 8 cycles, SYBR qPCR was used to determine total cycle numbers needed. Typically, a total of 12 additional PCR cycles of library amplification were added, depending on qPCR results. After validating library size on an Agilent TapeStation, 150-bp paired-end sequencing was performed by NovaSeq 6000 at Yale Center for Genome Sequencing.

first: Samuel

last: Weissman

first: Yang-Hui

middle: J

last: Yeh

first: Miriam

last: Viazmenski

first: Rachel

last: Kim

first: Jack

middle: A

last: Collora

first: Savannah

last: Steinhauser


title: HIV-1 transcription dominates over host gene activity at the HIV-1 integration site

type: Expression profiling by high throughput sequencing

overall_design: Triplicate RNA-seq profiling of Jurkat T cells infected with a single copy of replication-defective HIV-GFP, transduced with CRISPRa (dCas9-VP64 and MS2-P65-HSF1 transcription activator) or CRISPRi (dCas9-KRAB). Cell lines contain either nontargeting gRNA, HIV-targeting gRNA, or gRNA targeting the host gene containing the HIV integration site. RNA was isolated using Zymo Research Direct-zol kits (#R2056) and sequenced using NEB's rRNA-depletion and adapter ligation/Illumina sequencing protocol. Of note, the sequenced molecule is rRNA-depleted RNA.


title: FOCAS: Transcriptome-wide screening of individual m6A sites functionally dissects epitranscriptomic control of gene expression in cancer [FOCAS_4cellline_RNAseq]

city: Beijing

first: Jun

last: Liu

address: Haidian District

department: School of Life Sciences

country: China

institute: Peking University

summary: Although N6-methyladenosine (m6A) is a pervasive RNA modification essential for gene regulation, dissecting the functions of individual m6A sites remains technically challenging. To overcome this, we developed functional m6A sites detection by CRISPR-dCas13b-FTO screening (FOCAS), a CRISPR-dCas13b-based platform enabling high-throughput, site-specific functional screening of m6A. Applying FOCAS to four human cancer cell lines identified 4,475 m6A-regulated genes influencing cell fitness via both mRNAs and non-coding RNAs (ncRNAs), many of which are newly linked to cancer and exhibit dynamic developmental expression. FOCAS uncovered context-dependent and reader-specific effects of m6A within the same gene, revealing its intricate regulatory logic. We further uncovered universal and cell-type-specific m6A patterns with unique sites enriched in ncRNAs and universal ones in transcription-related genes. In SMMC-7721 cells we identified m6A-regulated transcriptional networks that demonstrated extensive epitranscriptome-transcriptome crosstalk. Overall, this study established a powerful, unbiased approach for the functional dissection of m6A, advancing the understanding of its complexity and therapeutic relevance in cancers.

overall_design: We analyzed the transcriptome expression in SMMC-7721-dCas13b-wtFTO cells, HepG2-dCas13b-wtFTO cells, HCT116-dCas13b-wtFTO cells and HeLa-dCas13b-wtFTO cells treated with sgRNAs.

first: Xinning

last: Zhang

first: Yifan

first: Xinyu


title: HTGTS-TCR-seq for profiling of mouse and human T-cell receptor α and β gene rearrangements and diversity

city: Shanghai

first: Haiqiang

last: Dai

address: 320 Yue Yang Road

institute: Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell  Science

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: A novel six-biomarker panel identified from male breast cancer-associated fibroblasts demonstrates prognostic power for prostate tumors

city: Rende

first: Rosamaria

last: Lappano

state: Cs

address: via P. Bucci

country: Italy

institute: University of Calabria

summary:
Background. Male breast cancer (BC) is rare, accounting for only approximately 1% of all cases of BC, and poorly characterized. In contrast, prostate cancer is the most prevalent cancer in men and serves as a model for understanding male-specific tumor biology. The advent of high-throughput technologies has enabled the development of gene expression signatures for both breast and prostate tumors that could inform prognosis and guide treatment. In this respect, the role of the tumor microenvironment, particularly cancer-associated fibroblasts (CAFs), remains largely underexplored. Here, we sought to identify a CAF-related gene signature in male patients with BC and prostate cancer to reveal specific protumorigenic mechanisms and identify novel therapeutic targets for both malignancies.
Methods. RNA sequencing was performed to analyze and compare the transcriptomes of CAFs isolated from female and male BC patients. Differentially expressed genes (DEGs) between female and male breast CAFs were identified and subjected to enrichment analyses. Using a set of candidate upregulated genes in male breast CAFs, K-means clustering of prostate cancer patients was performed using multiple datasets to define a prognostic gene signature. Kaplan‒Meier curves and log-rank tests were conducted to assess differences in patient outcomes and other clinical variables between groups of patients with high or low prognostic gene expression. The clustering results were then validated using decision tree analysis, and boosted calculations were employed to increase the classifier performance.
Results. Transcriptomic profiling revealed 775 DEGs between female and male breast CAFs. Owing to the limited transcriptomic data from male BC patients, we leveraged large prostate cancer cohorts to investigate the relevance of the genes expressed by male breast CAFs. A six-gene signature (ASPN, COL4A1, COL4A2, COL5A3, COMP and FN1) that could predict patient outcomes in multiple independent cohorts of prostate cancer patients was identified.
Conclusions. We identified a novel gene signature with strong prognostic value in prostate cancer and potential relevance to male BC. This gene signature represents a complementary tool to standard clinical parameters for improving patient stratification and management.

overall_design: Identification of a novel CAFs-related gene signature for male breast and prostate cancer patients.


title: Molecular responses in abdominal subcutaneous adipose tissue after a session of endurance exercise: effects of exercise intensity

city: Ann Arbor

first: Jeffrey

last: Horowitz

state: MI

address: 830 N University Ave

department: School of Kinesiology

institute: University of Michigan

summary: The primary aim of this study was to compare the acute effects of three exercise intensities on abdominal subcutaneous adipose tissue (aSAT) transcriptome in regular exercisers. A total of 45 adults who exercise regularly were assigned to perform a single session of either low-intensity continuous (LOW; 60min at 30% VO2max; n=15), moderate-intensity continuous (MOD; 45min at 65% VO2max; n=15), or high-intensity interval exercise (HIGH; 10x1min at 90% VO2max interspersed with 1min active recovery; n=15). aSAT biopsy samples were collected before and 1.5hours after the exercise session for bulk RNA sequencing and targeted protein immunoassays. HIGH upregulated genes involved in cytokine secretion, insulin signaling, and proteolysis while MOD and LOW upregulated genes regulating ECM remodeling, ribosome biogenesis, and oxidative phosphorylation pathways. Exercise-induced changes in aSAT angiogenic, MAPK cascade, and clock genes, ERK protein phosphorylation, and circulating cytokines were similar after all three exercise treatments. Network analysis identified exercise-responsive gene clusters linked to cardiometabolic health traits. Cell-type analysis highlighted a heterogeneous response of aSAT cell types to exercise, with distinct patterns observed across exercise intensities. Collectively, our data characterizes early responses in aSAT after a single session of exercise. Because adaptations to exercise training stem from an accrual of responses after each session of exercise, these early responses to exercise are likely important contributors to the long-term structural and functional changes that occur in adipose tissue in response to exercise training.

overall_design: Bulk RNA-seq profiling and targeted protein analysis on abdominal subcutaneous adipose tissue (aSAT) biopsy samples from regular exercisers before and 1.5 hours after one exercise session of three different intensities.

first: Cheehoon

last: Ahn

first: Tao

first: Thomas

last: Rode

first: Gayoung

last: Yang

first: Olivia

middle: K

last: Chugh

first: Sierra

last: Ellis

first: Sophia

last: Ghayur

first: Shirya

last: Mehta

first: Ryan

last: Salzman

first: Hui

last: Jiang

first: Stephen

middle: C

last: Parker

first: Charles

middle: F

last: Burant


title: Effects of α- and β-amylin on gene expression in mouse embryonic fibroblasts (MEFs)

city: Obu

first: Masataka

last: Sugimoto

state: Aichi

address: 7-430 Morioka-cho

department: Cellular Pathology

country: Japan

institute: National Center for Geriatrics and Gerontology

summary: α- and β-amyrin exhibit senolytic activity in MEFs. This study aimed to investigate the underlying pathways involved in this anti-senescent effect.

overall_design: Non-senescent (passage 1) and senescent (P6) MEFs were stimulated with α-amyrin (20 μM) or β-amyrin (20 μM) for 3 days. RNA expression was analyzed by RNA-sequencing.

first: Mikako

last: Hirose


title: FOCAS: Transcriptome-wide screening of individual m6A sites functionally dissects epitranscriptomic control of gene expression in cancer [FOCAS_MeRIP]

first: Jun

last: Liu

overall_design: Chromatin-associated RNA and total RNA m6A profiles of WT HepG2, HCT116 and HeLa cells were generated by deep sequencing, in duplicate.

first: Xinning

last: Zhang

first: Yifan

first: Xinyu


title: FOCAS: Transcriptome-wide screening of individual m6A sites functionally dissects epitranscriptomic control of gene expression in cancer [CRISPR screening]

overall_design: We conducted CRISPR screening in SMMC-7721-dCas13b-wt/mutFTO cells, HepG2-dCas13b-wt/mutFTO cells, HCT116-dCas13b-wt/mutFTO cells and HeLa-dCas13b-wt/mutFTO cells with dCas13b-FTO editing system. Cells were collected on 0 doubling time (Dt) and 14 Dt and subjected to next generation sequencing.


title: PyBo-seq of IVT RNA

city: Mainz

first: Alexandr

last: Gopanenko

address: Ackermannweg 4

country: Germany

institute: Institute of Molecular Biology gGmbH (IMB)

summary: The RNA modification 5-formylcytidine (f5C) is poorly explored in mammals. Low f5C levels reported in mRNA may reflect spurious 5-methylcytidine (m5C) oxidation or targeted demethylation by TET or ALKBH1 dioxygenases. Here we analyze f5C in RNA of mouse embryonic stem cells (mESCs) using LC-MS/MS and chemical-assisted sequencing. We reveal that the previously reported pyridine-borane-sequencing method misidentifies N4-acetylcytidine (ac4C) and unmodified, hyper-reactive cytidines in a CUMC context as f5C. To overcome these limitations, we developed FIBo-seq with enhanced specificity and sensitivity for f5C-sequencing. We find no evidence for a role of TET enzymes in generating f5C, unlike for ALKBH1. Moreover, no f5C sites are detectable in mRNA. Instead, the bulk of mammalian f5C resides in the well-established mitochondrial tRNA Methionine (mt-tRNAMet) and is mediated by ALKBH1. The results argue against an instructive function for f5C outside tRNA in mammals.

overall_design: Pyridine-borane-assisted RNA-sequencing (PyBo-seq) of synthetic, modification-free RNA generated by in vitro transcription (IVT) from poly(A)+ RNA of mESCs

first: Jasmin A.

last: Dehnen

first: Alexandr V.

first: Carola

last: Scholz

first: Michael U.

last: Musheev

first: Christof

last: Niehrs


title: Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal epitranscriptome

status: Public on Oct 22 2025

city: Rehovot

first: Miguel

middle: A.

last: Garcia-Campos

state: Center District

address: Herzl 234, Meyer Bldg., Room 1410

department: Molecular Genetics

country: Israel

institute: Weizmann Insitute of Science

sample_organism:
Pseudomonas aeruginosa
Escherichia coli
Bacillus subtilis
Acetivibrio thermocellus
Haloferax volcanii
Pyrococcus furiosus
Sulfolobus acidocaldarius
Thermoplasma acidophilum
Saccharomyces cerevisiae
Homo sapiens
Salmonella enterica
Pyrodictium abyssi
Thermococcus kodakarensis
Planococcus halocryophilus


title: Pilot FIBo-seq in Tet1/2/3 CTRL and TKO mESC

summary: The RNA modification 5-formylcytidine (f5C) is poorly explored in mammals. Low f5C levels reported in mRNA may reflect spurious 5-methylcytidine (m5C) oxidation or targeted demethylation by TET or ALKBH1 dioxygenases. Here we analyze f5C in RNA of mouse embryonic stem cells (mESCs) using LC-MS/MS and chemical-assisted sequencing. We reveal that the previously reported pyridine-borane-sequencing misidentifies N4-acetylcytidine (ac4C) and unmodified, hyper-reactive cytidines in a CUMC context as f5C. To overcome these limitations, we developed FIBo-seq with enhanced specificity and sensitivity for f5C-sequencing. We find no evidence for a role of TET enzymes in generating f5C, unlike for ALKBH1. Moreover, no f5C sites are detectable in mRNA. Instead, the bulk of mammalian f5C resides in the well-established mitochondrial tRNA Methionine (mt-tRNAMet) and is mediated by ALKBH1. The results argue against an instructive function for f5C outside tRNA in mammals.

overall_design: FIBo-seq (f5C-immunoprecipitation-pyridine-borane sequencing) of RNA from Tet1/2/3 control (CTRL) mouse embryonic stem cells (mESCs) and their corresponding Tet1/2/3 triple knockout (TKO) mESCs. Pilot experiment, no rRNA depletion.


title: PyBo-seq in Tet1/2/3 CTRL and TKO and Alkbh1 CTRL and KO mESCs,  Mal-seq in Alkbh1 CTRL and KO mESCs

overall_design:
Pyridine-borane-assisted RNA-sequencing (PyBo-seq) of Tet1/2/3 control (CTRL) mouse embryonic stem cells (mESCs) and their corresponding Tet1/2/3 triple knockout (TKO) mESCs.
PyBo-seq and malononitrile-assisted RNA-seq (Mal-seq) of Alkbh1 CTRL mESCs and their corresponding knockout (KO) mESCs.


title: FIBo-seq in Tet1/2/3 CTRL and TKO mESC

overall_design: FIBo-seq (f5C-immunoprecipitation-pyridine-borane sequencing) of RNA from Tet1/2/3 control (CTRL) mouse embryonic stem cells (mESCs) and their corresponding Tet1/2/3 triple knockout (TKO) mESCs.


title: FOCAS: Transcriptome-wide screening of individual m6A sites functionally dissects epitranscriptomic control of gene expression in cancer [RNA-Seq]

overall_design: We analyzed the transcriptome expression in SMMC-7721-dCas13b-wtFTO cells treated with sgRNAs.


title: Glucocorticoids unleash immune-dependent melanoma control through inhibition of the GARP/TGFβ axis [RNA-seq]

city: Manchester

first: Santiago

last: Zelenay

address: Wilmslow Rd, Manchester M20 4BX

country: United Kingdom

institute: Cancer Research UK Manchester Institute

summary: Glucocorticoids were found to trigger immune-dependent control of an orthotopic melanoma model. This was found to be dependent on glucocorticoid receptor expression in the tumor cells. We used whole exome RNAseq of parental and glucocorticoid receptor knockout tumor cells in vivo and in vitro to identify the transcriptional changes induced following glucocorticoid treatment.

overall_design: 10 mice were implanted with 20967 parental or 20967 GRKO melanoma tumours intradermally. 5 mice from each group were treated with control drug and 5 with glucocorticoid (clobetasol priopionate). These tumours were harvested, digested, RNA extracted, cDNA produced and sent for bulk sequencing. Additionally, 20967 parental and 20967 GRKO melanoma cells were cultured in vitro and treated with control (DMSO) or clobetasol propionate (1µM) prior to RNA collection and sequencing.

middle: H

last: Earnshaw

first: Agrin

last: Moeini

first: Richard

last: Reeves

first: Robert

last: Sellers

first: Sudhakar

last: Sahoo


title: FOCAS: Transcriptome-wide screening of individual m6A sites functionally dissects epitranscriptomic control of gene expression in cancer [FOCAS_GLORI]

overall_design: We detected the modification levels of m6A sites in SMMC-7721-dCas13b-wtFTO cells, HepG2-dCas13b-wtFTO cells, HCT116-dCas13b-wtFTO cells and HeLa-dCas13b-wtFTO cells treated with sgRNAs.


title: FOCAS: Transcriptome-wide screening of individual m6A sites functionally dissects epitranscriptomic control of gene expression in cancer [MeRIP-Seq]

type: Methylation profiling by high throughput sequencing

overall_design: Chromatin-associated RNA m6A profiles of WT SMMC-7721 cells were generated by deep sequencing, in duplicate.


title: FOCAS: Transcriptome-wide screening of individual m6A sites functionally dissects epitranscriptomic control of gene expression in cancer [ChIP-Seq]

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for H3K4me3 in SMMC-7721-dCas13b-wtFTO cells treated with sgRNAs.


title: Expression profiles in Chd7 knockdown astrocytes

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: Tebiro 6-10-1

department: New Projects Development Division

institute: Toray Industries,Inc.

summary: Chd7 is an ATP-dependent chromatin-remodeling enzyme. We performed a microarray analysis to examine changes in gene expression between control and Chd7 knockdown astrocytes. The results provide insight into the function of Chd7 in astrocytes.

overall_design: Astrocytes derived from P0 Chd7flox/flox mouse cortex were infected with control or Cre lentiviruses and were cultured with 10% FBS, FGF2, EGF, and B-27 supplement. Three days after infection, the virus-infected astrocytes were harvested.

first: Motoshi

last: Nagao


title: GDF-11 stimulates human extravillous trophoblast cell invasion by upregulating ANGPTL4 expression

city: Zhengzhou

first: Jung-Chien

last: Cheng

state: Henan

address: 40, Daxue Road

institute: The First Affiliated Hospital of Zhengzhou University

summary: Proper regulation of extravillous trophoblast (EVT) cell invasion is critical for normal placental development and function. Growth differentiation factor 11 (GDF-11), a member of the transforming growth factor-β (TGF-β) superfamily, has been shown to promote EVT cell invasion, yet the underlying molecular mechanisms remain largely unclear. In this study, RNA sequencing identified angiopoietin-like 4 (ANGPTL4), a multifunctional secreted protein, as a novel downstream target of GDF-11. In vitro experiments demonstrated that GDF-11 significantly upregulated ANGPTL4 expression in both HTR-8/SVneo cells and primary human EVT cells. Mechanistically, we found that the type I TGF-β receptors ALK4 and ALK5 were essential for mediating the stimulatory effect of GDF-11 on ANGPTL4 expression. Further analysis revealed that SMAD3, but not SMAD2, was the key transcription factor involved in this process. Using both loss- and gain-of-function approaches, we demonstrated that ANGPTL4 was required for GDF-11-induced EVT cell invasion. Importantly, serum levels of GDF-11 were markedly reduced in patients with preeclampsia (PE), a pregnancy disorder associated with shallow trophoblast invasion and poor placentation. Together, our findings uncover a previously unrecognized GDF-11-ANGPTL4 signaling axis that regulates EVT cell invasion and provide new insight into the pathophysiology of PE.

overall_design: HTR-8/SVneo cells were treated with 30 ng/mL GDF-11 for 3 hours

first: Ze

last: Wu

first: Lanlan

last: Fang

first: Xuan

last: Dang

first: Yiping

last: Yu

first: Beibei

last: Bi

first: Xiaoyu

last: Han

first: Ying-Pu

last: Sun


title: Diverse transcriptional alterations in V2a propriospinal neurons following spinal cord injury

city: Cincinnati

first: Steven

middle: Allen

last: Crone

state: OH

address: 3333 Burnet Ave, MLC 7007

department: Pediatric Neurosurgery

institute: Cincinnati Children's Hospital Medical Center

summary: The V2a neurons contribute significantly to recovery of locomotor and respiratory function after injury in animal models. We used single nucleus RNA sequencing of enriched cervical V2a neurons to analyze the diversity of these neurons and their response to spinal cord injury.

overall_design: Nuclei from Chx10Cre/+; ROSA26CAG-LSL-Sun1-sfGFP-Myc/+ mouse cervical spinal cords were isolated from uninjured mice or 5 days post C2 hemisection spinal cord injury. Fluorescence-activated nuclei sorting (FANS) was used to isolate V2a (GFP+) nuclei. The sorted nuclei were then subjected to single nucleus RNA sequencing using 10X Chromium 3v3.

first: Christina

last: Thapa


title: Long COVID involves activation of proinflammatory and immune exhaustion pathways

city: Boston

first: Dan

last: Barouch

state: MA

address: 3 Blackfan Cir

department: CVVR

institute: Beth Israel Deaconess Medical Center

summary: Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls (n = 35), acutely infected individuals (n = 54), convalescent controls (n = 24) and patients with LC (n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls (n = 20) and patients with LC (n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease.

overall_design: Blood samples were collected from 178 patients --- 120 of whom were previously infected with SARS-CoV-2, and suffering from known long COVID symptoms. Severity of long COVID was determeined by self-reporting, and validated by a clinician's assessment. PBMCs were harvested and RNA was extracted, and used for total RNA-seq.

first: Malika

last: Aid


title: Identification of Three New Rugose Small Colony Variants from a Pseudomonas aeruginosa Biofilm

city: Toledo

first: Erin

last: Prestwich

state: Ohio

address: 2801 W. Bancroft St.

department: Medicinal/Biological Chemistry

institute: University of Toledo

summary: Pseudomonas aeruginosa is a gram-negative, pathogenic, bacterium that produces biofilms containing phenotypically distinct subpopulations (Dodson et al., 2022). It was discovered that rugose small colony variants (RSCVs) were isolated with the biofilm subpopulations. RSCVs are hyper-biofilm producing bacterial mutants with increased antibiotic tolerance and are often found in chronic infections. When separating and characterizing the three biofilm cell subpopulations from a single P. aeruginosa PA14 biofilm, we discovered three novel RSCVs (denoted RSCV_1, RSCV_2, and RSCV_3). These RSCVs differed from stationary wild type (WT) PA14, the PA14 biofilm subpopulations, and between the RSCVs themselves. The observed phenotypic changes in the RSCVs included differences in cellular morphology, exopolysaccharide production, biosynthesis of virulence factors, biofilm formation, and antibiotic tolerance. Different molecules were ionized on the cell membranes of RSCVs and stationary phase WT PA14 using matrix assisted laser desorption ionization (MALDI) mass spectrometry. RNA sequencing analysis of stationary phase cells identified a high number of transcripts that were differentially expressed between the RSCVs and WT PA14 as well as between RSCV_1 and RSCV_3. The levels of the intracellular signaling molecule bis-(3′, 5′)-cyclic-dimeric-guanosine monophosphate (cyclic-di-GMP) were higher in all of the RSCVs compared to WT PA14 and significantly lower in RSCV_3 as compared to both RSCV_1 and RSCV_2.  Whole-genome DNA sequencing analysis revealed single-nucleotide deletions and single-nucleotide polymorphisms (SNPs) among the RSCVs and between the RSCVs to WT PA14. The detected differences in the RSCVs have significant implications for biofilm production, antibiotic tolerance, and virulence.

overall_design: Bulk RNA-seq profiling of RSCV_1 (n = 3), RSCV_3 (n = 3), and stationary phase WT PA14 (n = 3).

first: Benjamin

last: Smartnick

first: Eric

last: Carlson

first: Chase

middle: N

last: Morse

first: Taylor

last: Dodson

first: Nathan

last: Wamer

first: Avery

middle: M

last: Horne

middle: G


title: Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1 [array]

city: Vancouver

first: Aly

last: Karsan

address: 675 West 10th Avenue

country: Canada

institute: Canada's Michael Smith Genome Sciences Centre

summary:
Purpose: The goals of this study are to compare the transcriptome profile of human cord blood derived CD34+ cells expressing shRNA targeting FBXO11 or non-targeting shRNA by microarray.
Methods: mRNA profiles of CD34+ cord blood cells expressing non-targeting shRNA or shRNA targeting FBXO11 were generated by microarray sequencing.

overall_design: CD34+ cord blood expressing non-targeting shRNA or shRNA targeting human FBXO11.

first: Hayle

last: Kincross


title: SOX2 confers tumour permissiveness in a specific skin progenitor population

status: Public on Oct 20 2025

city: Glasgow

first: Patricia

last: Centeno

state: Scotland

address: Switchback Rd, Bearsden, Glasgow

institute: Beatson Institute for Cancer Research

summary: The skin’s continuous renewal relies on stem and progenitor cells, yet their differential susceptibility to oncogenic mutations in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Rapid cSCC development occurs in melanoma patients treated with BRAF inhibitors, driven by paradoxical MAPK activation. To model this in mice, we use two complementary approaches: HRASG12V with BRAFi to mimic paradoxical MAPK activation, and BRAFV600E, which drives MAPK hyperactivation without further treatment. We target these mutations to the interfollicular stem and differentiation-committed progenitors of the basal epidermis. While stem cells rapidly form tumours, progenitors exhibit long-latency resistance despite retaining mutations and repopulating the basal layer. Ultimately, both populations produce similar tumours, revealing a shared transformation programme. However, SOX2 is uniquely upregulated in tumours from the progenitor population. SOX2 is expressed in 20% of human cSCC, suggesting that it could mark tumours originating from committed progenitors. Here, we show that SOX2 overexpression in progenitors induces a stem-like state and renders this otherwise resistant population permissive to transformation.

overall_design: We conducted RNAseq in tumours driven by BRAFV600E expressed in the  IVL population in the presence and absence of SOX2 overexpressor

first: Centeno

last: Patricia P


title: RNA Sequencing dataset of Claudin-low Breast Cancer Cell Lines with Neuropilin-1 Knockdown

city: Brisbane

first: Colleen

last: Nelson

state: Queensland

address: 199 Ipswich Road

department: Institute of Health and Biomedical Innovation; Vancouver Prostate Centre

country: Australia

institute: Queensland University of Technology; University of British Columbia

summary: Triple-negative breast cancers (TNBC) are a particularly aggressive breast cancer subtype with poor prognosis and high relapse rates. Due to a lack of identified targeted therapies, chemotherapy currently remains as the primary treatment for TNBC. Approximately 25-39% of TNBC are claudin-low breast cancers, which are mainly defined by low expression of cell-cell adhesion proteins and enrichment of mesenchymal signatures. Functional studies have demonstrated the potential role of the transmembrane-coreceptor, Neuropilin-1 (NRP1) in regulating the progression of these tumours. However, there have been no high-throughput studies to date that comprehensively investigate NRP1-modulated cell signalling across multiple claudin-low cell lines. Therefore, we knocked-down NRP1 by two small-interfering RNA (siRNA) or two short-hairpin RNA (shRNA) sequences in each of HS578T, MDA-MB-231 and SUM159PT claudin-low cell lines and followed this with Bulk-RNA sequencing. We present this comprehensive transcriptomic data set which provides a valuable resource for the analysis of NRP1-regulated signalling pathways in claudin-low breast cancer, paving the way for future studies of its potential as a targeted therapeutic.

overall_design: 52 samples. 2-3 biological replicates of each treatment group. Three claudin-low breast cancer cell lines (HS578T, MDA-MB-231, SUM159PT) were treated with two siRNA and two shRNA sequences (3 and 5) that target NRP1, as well as respective non-targeting (NT) controls.

first: Layla-Rose

last: Lynam

first: Anja

last: Rockstroh

first: Melanie

last: Lehman

first: Marianna

last: Volpert

first: Brett

last: Hollier


title: Tackling the early lung graft immunity by preconditioning donors with corticosteroids

city: Jouy-en-Josas

first: Jouneau

last: Luc

address: Domaine de Vilvert

country: France

institute: INRA

summary: Though lung transplantation (LT) is increasingly used to treat end-stage lung diseases, the clinical outcomes are disappointing, underscoring the need for novel therapeutic strategies. Preclinical studies revealed the critical role of innate immunity in LT outcomes. While corticosteroid boluses are routinely given to recipients, we hypothesized that donor preconditioning with corticosteroid could improve early immune parameters, in the context of ongoing clinical trials exploring various preconditioning approaches. We used a cross-circulatory pig platform that consists in a donor lung placed extracorporeally and connected to the circulation of a recipient pig whose leukocytes are fluorescently labelled. Donor preconditioning reduced the presence of CD3pos T-cell in the graft from both the donor and recipient, and enhanced the anti-inflammatory profile of alveolar macrophages, at least during first 10 hours of donor-recipient interaction. The alveolar macrophages isolated from corticosteroid-preconditioned pig lungs exhibited decreased gene expression of T-cell attracting chemokines during the 10-hour reperfusion period, correlating with the reduced T-cell infiltration. Similarly, human lung macrophages showed lower expression of these T-cell-attracting chemokines and higher anti-inflammatory profiles upon corticosteroid treatment. Thus, the early immune status of lung grafts is improved by donor preconditioning with corticosteroids through macrophage-targeted mechanisms, holding promises for enhanced clinical outcomes.

overall_design: scRNA-seq of MHC class II-positive cells from one pig lung

first: Isabelle

last: Schwartz-Cornil

first: Claudia

last: Bevilacqua

first: Thien-Phong

last: Vu-Manh

first: Ludivine

last: Soubigou-Taconnat

first: Clément

last: Pichot

first: Yann

last: JASZCZYSZYN

first: Luc

last: Jouneau


title: C9orf72 hexanucleotide repeat expansions impair microglial response in models of ALS

city: Antwrepen

first: Renzo

last: Mancuso

address: Universiteitsplein 1

country: Belgium

institute: Vlaams Instituut voor Biotechnologie

overall_design: Refer to individual Series


title: Single-cell RNA sequencing of pulmonaly pleomorphic carcinoma

city: Okayama

first: Shuta

last: Tomida

state: Okayama

address: 2-5-1 Shikata-cho, Kita-ku

department: Center for Comprehensive Genomic Medicine

institute: Okayama University Hospital

summary: Single-cell RNA sequencing (scRNA-seq) of pulmonary pleomorphic carcinoma (PPC) patients was conducted using the 10x Genomics platform to reveal the clonal evolution of PPCs.

overall_design: Surgically resected fresh frozen primary PPC samples from four patients were used. After tissue fixation and dissociation, library preparation was processed according to the Chromium Fixed RNA Profiling Reagent Kits for Multiplexed Samples.

first: Atsushi

last: Matsuoka

first: Kazuhiko

last: Shien


title: Spatial transcriptomics of pulmonary pleomorphic carcinoma

summary: Spatial transcriptomics of Pulmonary Pleomorphic Carcinoma (PPC) patients were conducted using the GeoMx Digital Spatial Profiler to reveal intratumoral heterogeneity of PPCs at molecular level. Hybridization was performed using the Human Whole Transcriptome Atlas, targeting human protein-coding transcripts.

overall_design: In this study, 125 Regions of Interest (ROIs) were selected from nine PPC patients based on pathologically defined tumor components (epithelial and sarcomatoid), adjacent normal lung tissue and mediastinal lymph node metastasis. As a sub-analysis, we performed region segmentation based on the presence or absence of the morphology marker CD45 and analyzed the tumor immune microenvironment.


title: C9orf72 hexanucleotide repeat expansions impair microglial response in models of ALS [scRNA]

summary: The involvement of microglia and neuroinflammation in amyotrophic lateral sclerosis (ALS) is well recognized, but the precise underlying molecular mechanisms remain elusive. We generated single-nuclei transcriptomic profiles from the spinal cord and motor cortex of sporadic (sALS) and C9orf72 (C9-ALS) ALS patients. We confirmed that C9orf72 is highly expressed in microglia and observed that the hexanucleotide repeat expansion (HRE) results in haploinsufficiency specifically in these cells. Whereas sALS microglia transitioned towards classically defined disease-associated transcriptomic profiles, C9orf72 HRE microglia exhibited a diminished response, with alterations in phagocytic and lysosomal pathways. We confirmed these observations using a human microglia xenograft model, which showed that C9orf72 loss-of-function leads to a reduced baseline activation, with lower expression of antigen-presenting related genes. We also confirmed the alterations in the endolysosomal pathway in C9orf72-HRE and C9orf72-deficient induced pluripotent stem cell (iPSC)-derived microglia. In addition, we observed a diminished response of astrocytes in C9orf72-HRE carriers and provided an extensive map of dysregulated ligand-receptor pairs in microglia and astrocyte indicating an altered cell-cell communication in both C9orf72 and sALS. This complex cellular interplay highlights variations in the cellular substrate of sporadic and inherited forms of ALS, providing valuable insights for patient stratification and for selecting appropriate treatments.

overall_design: iPSC' derived microglia were either sequenced for bulk RNA sequencing, or xenotransplanted into the mouse brain of Rag2-/- hCSF1KI with either a C9of72 KO or C9orf72 hexanucleotide repeat expansion cell line and their controls. Mice were sacrificed at 3 and 6 months.

first: Pegah

last: Masrori

first: Baukje

last: Bijnens

first: Laura

last: Fumagalli

first: Kristofer

last: Davie

first: Suresh Kumar

last: Poovathingal

first: Tim

last: Meese

first: Annet

last: Storm

first: Nicole

last: Hersmus

first: Raheem

last: Fazal

first: Diede

last: van den Biggelaar

first: Bob

last: Asselbergh

first: Roxane

last: Gruel

first: Johanna

last: Van Den Daele

first: Heidi

last: Denton

first: Paula

last: Polanco Miquel

first: Simona

last: Manzella

first: Winnok H.

last: De Vos

first: Siddarthan

last: Chandran

first: Ludo

last: Van Den Bosch

first: Dietmar Rudolf

last: Thal

first: Philip

last: Van Damme


title: Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1

first: Aly

last: Karsan

summary: Acute myeloid leukemia (AML) is an aggressive cancer with very poor outcomes. To identify additional drivers of leukemogenesis, we analyzed sequencing data from 1,727 unique individual patients with AML, which revealed mutations in ubiquitin ligase family genes in 11.2% of samples from adult patients with AML with mutual exclusivity. The SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase complex gene, FBXO11, was the most significantly downregulated gene of the SCF complex in AML. We found that FBXO11 interacts with and catalyzes K63-linked ubiquitination of LONP1 in the cytosol, to promote LONP1 entry into mitochondria. We show that depletion of FBXO11 or LONP1 reduced mitochondrial respiration through impaired LONP1 chaperone activity to assemble electron transport chain Complex IV. Reduced mitochondrial respiration secondary to FBXO11 or LONP1 depletion imparted myeloid-biased stem cell properties in primary CD34+ hematopoietic stem and progenitor cells (HSPCs) in vitro. In a human xenograft model, depletion of FBXO11 cooperated with AML1-ETO and mutant KRASG12D to generate serially transplantable AML. Our findings suggest that reduced FBXO11 cooperates to initiate AML by priming HSPC for myeloid-biased self renewal through attenuation of LONP1-mediated regulation of mitochondrial respiration.


title: C9orf72 hexanucleotide repeat expansions impair microglial response in models of ALS [RNA]

first: Renzo

last: Mancuso

first: Pegah

last: Masrori

first: Baukje

last: Bijnens

first: Laura

last: Fumagalli

first: Kristofer

last: Davie

first: Suresh Kumar

last: Poovathingal

first: Tim

last: Meese


title: RNA next-generation sequencing of cardiac fibroblasts isolated from young and old mice 7 days post-MI

city: Bucharest

first: Evelyn-Gabriela

last: Nastase-Rusu

state: Romania

address: B.P. Hasdeu St

country: Romania

institute: The Institute of Cellular Biology and Pathology "Nicolae Simionescu"

summary: Despite recent advances in pre-clinical research on cardiac remodeling following myocardial infarction (MI), the precise molecular pathways remain poorly understood, and effective therapies for heart failure are still delayed in development. The use of young animal models fails to mirror the clinical scenario of aged human patients, as aging is associated to less well-defined cellular identities that can alter the overall picture of cardiac repair. Here, we explore the active role of cardiac fibroblasts in post-MI ventricular remodeling, aiming to identify fibroblast-specific pathways through the lens of aging that enhance translational relevance. Cardiac fibroblasts were isolated from mice with MI through 5 day-culture of total interstitial population of cardiac cells under fibroblast-favoring conditions. The expression profiling of these cells was conducted as the initial approach to depict fibroblasts-specific changes that are common to young and old animals. For a translational perspective of the study, a group of young animals that endured MSC therapy after MI surgery was also included, to help identify the molecular changes that are amenable for therapeutic modulation. This analysis revealed GLIPR1 as being activated in cardiac fibroblasts within the infarct zone during the maturation phase post-MI, thus suggesting a role in the fibrotic process. Further investigations indicated that the inflammatory environment post-MI induced the upregulation of GLIPR1 in the myofibroblast subpopulation of infarcted cardiac fibroblasts, which promoted matrix reorganization by increase in TIMP3 expression. Our study shows a key role of GLIPR1 in modulating the matrix remodeling during cardiac repair post-MI. The data presented here provide a fundamental cellular and molecular knowledge that paves the way for further exploration of GLIPR1 as a potential therapeutic target to reduce cardiac fibrosis.

overall_design: mRNA profiles of cardiac fibroblasts isolated either from normal mice or after 7 days post-myocardial infraction (MI) and spited intro 6 experimental groups: Young-no-MI operated mice (5 biological replicates), Young-Sham-MI (5 biological replicates), Young-MI (5 biological replicates), Young-MI+MSC (5 biological replicates), Old-Sham (2 biological replicates) and Old-MI (3 biological replicates) C57Bl/6J mice were generated by next-generation sequencing.

first: Alexandrina

last: Burlacu

first: Catalina I.

last: Marinescu-Colan

first: Evelyn

last: G Nastase-Rusu

first: Bogdan

last: Preda

first: Laudy

last: Cherry


title: In vivo model of progressive tumor development in the anorectal transition zone (TZ)

city: Bron

first: Hector

last: Hernandez-Vargas

state: Rhone

address: 36 bis Rue de la Batterie

institute: Genomics Consulting

summary: Epithelial junctions are areas of associated pathology in human and mouse. In the case of the anorectal junction there is an abrupt transition from a simple columnar to a stratified squamous epithelium. To identify new regulatory mechanisms during injury and tumorigenesis, we studied this so called anorectal transition zone (TZ) at the single cell level. To this end, we took advantage of a mouse injury model where TZ cells are traced with fluorescent kerating 17 (K17CreER T2 x LSL-EGFP) at different points during transformation.

overall_design: Anorectal TZ cells were isolated by Fluorescence-activated cell sorting (FACS) and analyzed using scRNAseq.

first: Geraldine

last: Guasch

first: Chloe

last: Petitpas


title: A platelet transcriptomic signature of thromboinflammation predicts cardiovascular risk

city: New York

first: Jeffrey

last: Berger

state: NY

address: 435 E. 30th Street  Science Building, 723L

department: Department of Cardiology

institute: NYU Langone Health

summary: The CHOlesterol Reduction and Residual Risk in type 2 Diabetes (CHORD) study was a prospective study that investigated the effect of lipid lowering therapieis in participants with LDL-C >100 mg/dL without cardiovascular disease, off all antiplatelet therapy. Individuals with MPA levels, defined as CD14+CD16+ cells, were measured before and after four weeks of lipid lowering therapy. Patients were categorized as MPAhigh or MPAlow based on consistently high or low MPA levels accross timepoints. MPAhigh individuals exhibited an enrichment of immune signaling pathway. We developed a 42/gene Thromboinflammation Platelet Signature (TIPS), which correlated with MPA levels in multiple cohorts. TIPS was significantly elevated in patients with COVID-19 and myocardial infarction and predicted future cardiovascular events in patients who underwent lower extremity revascularization after a median follow-up of 18 months. Notably, TIPS was modifiable by ticagrelor. These findings introduce TIPS as a novel platelet RNA signature that captures platelet-immune activity and offers a promising tool for cardiovascular risk stratification.

overall_design:
RNA-seq profiling of platelets in individuals with LDL >120mg/dl before and four weeks after lipid-lowering medication
The current dataset represents 'baseline visit' samples.

middle: S

first: Matthew

last: Muller

first: Antonia

last: Beitzen-Heineke


title: Viral-directed augmentation of Kupffer cell cross-presentation provokes anti-tumor immunity against liver metastasis

city: Hefei

first: Chen

last: Chen

address: huang shan Road 443

institute: university of science and technology of china

summary: Liver metastasis is associated with poor prognosis and resistance to immune checkpoint inhibitors. Functional modulation of Kupffer cells (KCs) holds promise as an alternative immunotherapeutic approach. Leveraging their ability to capture circulating virions, we developed an oncolytic virus-based KC-targeting strategy that demonstrates efficacy and safety in treating multifocal liver metastasis. A single intravenous infusion of the M51R mutant vesicular stomatitis virus (VSV-M51R), but not wild-type (WT) VSV, induced significant tumor regression in mouse models of melanoma and colorectal cancer liver metastasis. The ineffectiveness of VSV-WT was ascribed to its rapid induction of KC apoptosis, whereas VSV-M51R transiently replicated within KCs without compromising their viability. Depleting KCs abolished the therapeutic effects of VSV-M51R. Mechanistically, VSV-M51R treatment promoted KCs proliferation in tumor-adjacent areas, enhancing their access to tumor foci, uptake of tumor-derived materials, and cross-presentation of tumor antigens, leading to a robust activation of hepatic anti-tumor CD8+T cell responses that required MAVS-dependent type I interferon triggering of KCs. Simultaneous blockade of PD-L1, which was upregulated on KCs during VSV-M51R treatment, achieved remarkable synergistic efficacy in late-stage liver metastasis. Our findings underscore the pivotal role of KCs in systemic oncolytic virotherapy and offers a potentially clinically applicable strategy for treating advanced liver metastasis.

overall_design: RNA-seq profiling of Kupffer cells isolated from metastatic B16F10 melanoma-bearing mice that were either untreated or treated with VSV-M51R for 3 days.

first: Qing

last: Zhang

first: Jiajia

last: Li

first: Xia

last: Zhou

first: Jizhou

last: Wang

first: Daxing

last: Gao

first: Lu


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

city: Cambridge

first: Walter

last: Lenoir

address: 301 Binney St

institute: Kronos Bio

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


title: p300 catalytic inhibition selectively targets IRF4 oncogenic activity in multiple myeloma (MM1S_KB528_timeseries)

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

overall_design: MM.1S cells at 0 (DMSO), 1, 3, 6, and 24 hour treated with 100 nM KB528 (p300 KAT inhibitor).

first: Marek

last: Kobylarz

first: Michelle

last: Shum

first: W

first: Pete

last: Rahl


title: p300 catalytic inhibition selectively targets IRF4 oncogenic activity in multiple myeloma (PBMC_KB528_timeseries)

overall_design: PBMC cells at 0 (DMSO), 1, 3, 6, and 24 hour treated with 100 nM KB528 (p300 KAT inhibitor).


title: p300 catalytic inhibition selectively targets IRF4 oncogenic activity in multiple myeloma (RPMI8226_KB528_timeseries)

overall_design: RPMI-8226 cells at 0 (DMSO), 1, 3, 6, and 24 hour treated with 100 nM KB528 (p300 KAT inhibitor).


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

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


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

city: Sdyney

first: Yanran

last: Zhao

address: Sydney NSW 2033

institute: UNSW

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

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

first: Jerome

last: Samir

first: Hui

first: Fabio

last: Luciani

first: Andrew

last: Lloyd


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

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

first: Wayne

last: Glore


title: Multi-modal Omics Analysis of a Paediatric Melanoma Highlights Mechanisms Underlying Treatment Resistance [Seq]

city: Augsburg

first: Pascal

middle: David

last: Johann

address: Stenglinstrasse 2

department: Paediatric Oncology

institute: University Hospital Augsburg

summary:
Background
Cutaneous malignant melanoma is a common cancer in adults but extremely rare in young children, affecting fewer than one child per million each year in Europe. Because of its rarity, most treatments for children are adapted from adult therapies, despite possible biological differences. This study aimed to explore the molecular features of a rare and aggressive melanoma in a 16-month-old patient to understand disease progression and treatment resistance.
Methods
We studied the tumour and metastases of a patient with a melanoma carrying an NRAS mutation, who received chemotherapy and immune checkpoint inhibitor treatment. The patient died 10 months after diagnosis. We used DNA methylation analysis, single nucleus RNA sequencing, and deep spatial transcriptomic profiling to examine genetic changes, gene activity, and their spatial distribution in both the primary tumour and lymph node metastases.
Results
Here we show that the tumour displayed high genetic and transcriptomic diversity. We identified increases in MITF and BRAF gene copies as likely key drivers of the aggressive disease, which were not detected at diagnosis. We also found activation of biological pathways, including VEGFA and WNT signalling, and abnormal activity of several genes linked to immune therapy response, with marked variation between tumour regions.
Conclusions
This case demonstrates that paediatric melanoma can harbour complex and spatially variable molecular changes that contribute to rapid disease progression and treatment failure. Our findings support incorporating detailed spatial transcriptional profiling into clinical assessment to better guide therapy in rare paediatric cancers.

overall_design: The submission includes multiple datasets generated from the same samples, from one patient. The datasets include: 1. Spatial transcriptomics (GeoMx DSP) of the primary tumour, lymph node metastasis, healthy lymph node and recurrence.   2. single nucleus RNA-Seq (10X Genomics) of the primary tumour (hg38, 2020-A).

first: Marlena

last: Mucha

first: Sebastian

last: Buehner

first: Maurice

last: Lossner

first: Victoria

middle: E

last: Fincke

first: Nic

last: Reitsam

first: Felix

last: Dorn

first: Dajana

last: Lobbes

first: Katharina

last: Gastberger

first: Tobias

last: Schuster

last: Dintner

first: Christopher

last: Schroeder

first: Ines

middle: B

last: Brecht

first: Bruno

last: Maerkl

first: Michael

last: Fruehwald

middle: D


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

city: Oslo

first: Yohan

last: Lefol

state: Oslo

address: Sognsvannsveien 20 Rikshospitalet

department: Institute of Clinical Medicine

country: Norway

institute: University of Oslo

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

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

first: Diana

last: Bordin

first: Garry

last: Wong

first: Nurye

last: Tekin

first: Junbai

last: Wang


title: Inhibition of CXCL10 and IFN-γ ameliorates myocarditis in preclinical models of SARS-CoV- 2 mRNA vaccination

city: Stanford

first: Joseph

middle: C.

last: Wu

state: California

address: 240 Pasteur Dr

department: Stanford Cardiovascular Institute

institute: Stanford university

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

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

first: Xu

last: Cao

first: Masataka

last: Nishiga

first: Amit

last: Manhas

first: Arianne

last: Caudal

first: Gema

last: Mondejar-Parreño

first: Shane

middle: R

last: Zhao

first: James

middle: W

last: Jahng

first: Mingqiang

first: Paul

last: Utz

first: Kari

last: Nadeau


title: Multi-modal Omics Analysis of a Paediatric Melanoma Highlights Mechanisms Underlying Treatment Resistance [methylation]

first: Pascal

last: Johann

overall_design: The submission includes DNA methylation profiling by Illumina EPIC v2 array of primary tumour, healthy lymph node and lymph node metastasis from the paediatric melanoma patient.

first: Marlena

last: Mucha

first: Sebastian

last: Buehner

first: Maurice

last: Lossner

first: Victoria

last: Fincke

first: Nic

last: Reitsam

first: Felix

last: Dorn

first: Dajana

last: Lobbes

first: Katharina

last: Gastberger

first: Tobias

last: Schuster

last: Dintner

first: Christopher

last: Schroeder

first: Ines

last: Brecht

first: Bruno

last: Maerkl

first: Michael


title: SOX2 confers tumour permissiveness in a specific skin progenitor population.

first: Patricia

last: Centeno

summary: The skin’s continuous renewal relies on stem and progenitor cells, yet their differential susceptibility to oncogenic mutations in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Rapid cSCC development occurs in melanoma patients treated with BRAF inhibitors, driven by paradoxical MAPK activation. To model this in mice, we use two complementary approaches: HRASG12V with BRAFi to mimic paradoxical MAPK activation, and BRAFV600E, which drives MAPK hyperactivation without further treatment. We target these mutations to the interfollicular stem and differentiation-committed progenitors of the basal epidermis. While stem cells rapidly form tumours, progenitors exhibit long-latency resistance despite retaining mutations and repopulating the basal layer. Ultimately, both populations produce similar tumours, revealing a shared transformation programme. However, SOX2 is uniquely upregulated in tumours from the progenitor population. SOX2 is expressed in 20% of human cSCC, suggesting that it could mark tumours originating from committed progenitors. Here, we show that SOX2 overexpression in progenitors induces a stem-like state and renders this otherwise resistant population permissive to transformation.

overall_design: We conducted RNAseq in tumours driven by BRAFV600E expressed in the K5, K14 and IVL population and in normal skin.

first: Patricia P


title: Gene expression of ISG15-treated immortalized fibroblasts

city: Miaoli County

first: Ya-Wen

last: Chen

address: 35, Keyan Rd, Zhunan Town

department: National Institute of Cancer Research

country: Taiwan

institute: National Health Research Institutes

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

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

first: Ssu-Han

last: Wang

first: Yu-Lin


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

status: Public on Oct 19 2025

city: Beijing

first: Suijuan

last: Zhong

state: Haidian

address: No.19 Xinjiekouwai Street

institute: Beijing Normal University

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

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

first: Qian

last: Wu


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

first: Hua

address: 38 Xueyuan Rd

institute: Peking University

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

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


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

first: Walter

last: Lenoir

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

first: Marek

last: Kobylarz

first: Michelle

last: Shum

first: Frank

first: Pete

last: Rahl

first: Wayne

last: Glore


title: DNA methylation profiling of human CD4+ T helper cells reveals the epigenetic control of SLAMF7 expression in IFN-γ producing cells

city: Braunschweig

first: Jochen

last: Huhn

address: Inhoffenstraße 7

institute: HZI - Helmholtz-Zentrum für Infektionsforschung GmbH

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

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

first: Saumya

last: Kumar

first: Anna

last: Ntalli

first: Stefan

last: Floess

last: Huehn


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

city: Jerusalem

first: Alana

last: Amelan

address: 9 Wolfson Boulevard

department: Genetics

institute: The Hebrew University of Jerusalem

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

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

first: Stephan

last: Collins

first: Nadirah

last: Damseh

first: Nanako

last: Hamada

first: Ahd

last: Salim

first: Elad

last: Dvir

first: Galya

last: Monderer-Rothkoff

first: Tamar

last: Harel

first: Koh-ichi

last: Nagata

first: Binnaz

last: Yalcin

first: Sagiv

last: Shifman


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

status: Public on Oct 17 2025

city: Ann Arbor

first: Poulami

last: Dey

address: 1301 Catherine St

institute: Michigan Medicine

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

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

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

last: Gudjonsson

first: Lam

last: Tsoi


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

status: Public on Oct 18 2025

city: Nanjing

first: Zhenji

last: Gan

address: 12 Xuefu Road

department: Model Animal Research Center of Nanjing University

institute: Nanjing University

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

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

first: Chenyun

last: Ding


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

first: Walter

last: Lenoir

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

first: Marek

last: Kobylarz

first: Michelle

last: Shum

first: W

first: Pete

last: Rahl


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

city: Iowa City

first: Damian

middle: J

last: Krysan

state: IA

address: 25 South Grand, 2040 ML

department: Division of Pediatrics & Infectious Disease

institute: University of Iowa Hospitals and Clinics

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

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

first: Juraj

last: Kramara

first: Rohan

last: Wakade

first: Corey

last: Frazer

first: Mark

middle: A

last: Stamnes

first: Richard

last: Bennett


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

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

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


title: Multi-kinase inhibition of STE20 kinases is neuroprotective against chemotherapy-induced axon degeneration

city: Los Angeles

first: Riki

last: Kawaguchi

state: CA

address: 760 Westwood Plaza, Room 37-420

department: Department of Psychiatry and Neurology Department of Psychiatry

institute: University of California, Los Angeles

summary: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition resulting from the toxic action of cancer therapies on peripheral neurons. CIPN features axon terminal retraction from target organs leading to a myriad of sensory symptoms such as mechanical and thermal insensitivity, tingling, numbness and burning pain. There are currently no preventative or curative treatments, mostly because the mechanisms leading to axon degeneration upon chemotherapy treatment in humans remain largely unknown. We developed a model of CIPN suitable for high-throughput screening that involves progressive axon degeneration culminating in the death of human iPSC-derived sensory neurons exposed to paclitaxel. Using this model, we screened a library of 192 kinase inhibitors and identified 19 neuroprotective compounds. The top neuroprotective compounds all inhibited members of the STE20 family of kinases; MAP4K4, MAP4K6, and MAP4K7. Genetic and pharmacological inhibition confirmed that simultaneous, but not individual, inhibition of these three kinases is necessary for protection against paclitaxel-induced axonal toxicity in our model, and also in human primary DRG neurons. Importantly, pharmacological inhibitors specific to the STE20 family of kinases did not prevent paclitaxel-mediated killing of three breast cancer cell lines. Transcriptomic studies revealed that it was inhibition of the JNK-c-Jun pathway that prevented cell death and inhibition of the MAP4K-p38 axis that rescued axon degeneration. STE20 kinases are, therefore, a potential therapeutic target for mitigating paclitaxel-induced axon degeneration in sensory neurons while maintaining the therapeutic effects of chemotherapy in cancer patients.

overall_design:
28DIV iPSC-derived sensory neurons are treated for 24hrs with paclitaxel in the presence of STE20 inhibitor (GNE-495) to prevent axon degeneration or in the presence of JNK inhibitor (JNK-IN-8) to prevent cell death
GSE298389_ProcessedData.xlsx has data for samples GSM9013321-GSM9013356
GSE298389_ProcessedData2.xlsx has data for samples GSM9345116-GSM9345163

first: Veselina

last: Petrova

first: Qing

last: Wang

first: Clifford

last: Woolf


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

city: Exeter

first: Steven

last: West

state: Devon

address: Stocker Rd

department: Living Systems Insitute

institute: University of Exeter

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

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

first: Chris

last: Estell

first: Krystian

last: Łazowski

first: Joshua

last: Eaton


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

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


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

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


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

city: Turin

first: Andrea

last: Lauria

address: Via Accademia Albertina, 13

department: Life Sciences and Systems Biology

institute: University of Turin

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

overall_design: Refer to individual Series

first: Irene

last: Zorzan

first: Elena

last: Carbognin

first: Valentina

last: Proserpio

first: Mattia

last: Arboit

last: Paolucci

last: Drusin

first: Monika

last: Sledziowska

first: Salvatore

last: Oliviero

first: Graziano

last: Martello


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

type: Non-coding RNA profiling by high throughput sequencing

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


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

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


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

city: Sapporo

first: Issei

last: Kawakita

state: Hokkaido

address: N14 W5, Kita-ku

department: Graduated school of Medicine

institute: Hokkaido University

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

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

first: Shohei

last: Honda

first: Yuta

last: Yamada

first: Shugo

last: Tanaka

first: Yuko

last: Katayama

first: Takeshi

last: Shionoiri

first: Asuka

last: Ishii

first: Hiroyuki

last: Kurosu

first: Kazuya

last: Hamada

first: Kentaro

last: Kumagai

first: Kensuke

last: Nakazono

first: Rino

last: Saito

first: Chihiro

last: Terasaka

first: Ryo

last: Takahashi

first: Insu

last: Kawahara

first: Momoko

last: Ara

first: Sari

last: Iwasaki

first: Satoshi

first: Atsushi

last: Niida

first: Eiso

last: Hiyama

first: Akinobu

last: Taketomi

first: Koji

last: Taniguchi


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

city: Paris

first: Robin

last: Rondon

address: 15 rue Hélène Brion

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

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

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

first: Théaud

last: Hezez

first: Julien

last: Richard Albert

first: Shinichiro

last: Hayashi

first: Bernadette

last: Drayton-Libotte

first: Gloria

last: Gonzalez Curto

first: Frédéric

last: Auradé

first: Elie

last: Balloul

first: Claire

last: Dugast-Darzacq

last: Relaix

first: Pascale

last: Gilardi-Hebenstreit

first: Vanessa

last: Ribes


title: Probing DNA damage sites reveals context-dependent and novel DNA damage response factors

status: Public on Oct 16 2025

city: Utrecht

first: Tuncay

last: Baubec

address: Padualaan 8

department: Department of Biology

country: Netherlands

institute: Utrecht University

summary: DNA damage is a constant threat to genome integrity and function. Diminished capacity for DNA repair is linked to many human diseases, therefore, understanding the molecular pathways responding to DNA damage is key for developing novel therapies. Lack of unbiased probes to report DNA damage dynamics in living cells and animals limits our current efforts to completely understand DNA repair processes. In this study, we overcome these limitations by engineering protein probes containing the tandem-BRCT domain of MCPH1, which we show to have a specific affinity for the DNA-damage-associated histone mark H2AX. We employ these probes to track DNA damage dynamics in living cells exposed to a panel of different genotoxic insults, to visualize DNA damage targeted to heterochromatinised satellite repeats, and to map DNA double strand breaks genome-wide. Finally, we highlight the versatility of our probe to visualize programmed double strand breaks during gametogenesis in C. elegans. Taken together, we present a novel protein probe with broad application potential for DNA damage research.

overall_design: Antibody ChIP sequencing was performed in 4-hydroxytamoxifen- and DMSO-treated U2OS DIvA cells


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

city: Toyama

first: Naoya

last: Kitamura

state: Toyama

address: 2630, Sugitani

department: Thoracic Surgery

institute: University of Toyama

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

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

first: Mayumi

last: Iwatake

first: Satoshi

last: Mizoguchi

first: Shadil

last: Wani

first: Komei

last: Kobayashi

first: Muhammad

last: Hasnain

first: Dung

middle: V

last: Nguyen

first: Ryo

last: Yokoyama

first: Naru

last: Kitade

first: Toshihiro

last: Ojima

first: Koichiro

last: Shimoyama

last: Koba

first: Hideki

last: Hatta

first: Micha Sam

last: Raredon

first: Kenichi

last: Hirabayashi

first: Yoshitomo

last: Morinaga

first: Tomoshi

last: Tsuchiya