title: Spatiotemporal regulation of arbuscular mycorrhizal symbiosis at cellular resolution [MC]

city: Cambridge

first: Gabriel

last: Ferreras-Garrucho

state: Cambridgeshire

address: 93 Lawrence Weaver Rd

department: Crop Science Centre, Department of Plant Sciences

institute: University of Cambridge

summary: Arbuscular mycorrhizal (AM) symbiosis develops through successive colonization of root epidermal and cortical cells, culminating in the formation of arbuscules, tree-like intracellular structures that are transient yet essential sites of nutrient exchange. To dissect the cellular and structural complexity of AM establishment in rice roots colonized by Rhizophagus irregularis, we applied dual-species spatial transcriptomics to simultaneously monitor plant and fungal gene expression at single-cell resolution. This approach revealed surprising differences in transcriptional activity between fungal structures and showed that morphologically similar arbuscules can be transcriptionally distinct. These findings suggest hidden functional diversity among arbuscules, indicating that nutrient exchange is not uniform but finely modulated across individual structures. Because arbuscules form and degenerate within only a few days, we further sought to capture translational regulation across their life span. We pioneered AM-inducible TRAP-seq (Translating Ribosome Affinity Purification followed by RNA-seq) using stage-specific promoters, enabling cell-type- and stage-resolved profiling for the first time in AM symbiosis. This revealed extensive spatiotemporal reprogramming of nutrient transport and signaling, with distinct sets of phosphate, nitrogen, and carbon transporters and regulators upregulated or repressed at different stages of arbuscule development, suggesting that nutrient exchange is dynamically regulated across the arbuscule life cycle. More broadly, cell wall biosynthesis genes and key defence markers were suppressed during arbuscule formation, whereas upon collapse, defence markers were strongly upregulated, suggesting a host-driven shift towards symbiosis termination. Together, these findings highlight the nuanced and dynamic regulation of AM symbiosis at cellular resolution, refining our understanding of how nutrient exchange and fungal development are coordinated in space and time, and providing a framework for further functional exploration.

sample_organism:
Oryza sativa
Rhizophagus irregularis

overall_design: Molecular Cartography (Resolve Biosciences), using a panel of 100 probes against transcripts of Oryza sativa (rice) and the arbuscular mycorrhizal fungus Rhizophagus irregularis, for crown roots (CR) and large lateral roots (LLR) of rice either colonised (+Ri) or not colonised (-Ri) by R. irregularis at 6 weeks post-inoculation.

first: Tania

last: Chancellor

first: Garo

last: Akmakjian

first: Héctor

last: Montero

first: Emma

last: Wallington

first: Samik

last: Bhattacharya

first: Christian

last: Korfhage

first: Julia

last: Bailey-Serres

first: Uta

last: Paszkowski


title: Functional characterization of Central Nervous System (CNS) and peripheral immune responses in Alzheimer's Disease after Bacillus Calmette Guerin (BCG) vaccination in older adults.

status: Public on Apr 27 2026

city: Charlestown

first: Mahesh Chandra

last: Kodali

state: MA

department: Neurology

country: USA

institute: Massachusetts General Hospital / Harvard Medical School

type: Expression profiling by high throughput sequencing

summary: Cerebrospinal Fluid cells collected from older adults before and after BCG vaccination were studied for evaluating celltype specific functional responsivity to stimulation with antigens. Peripheral blood mononuclear cells were also studied to compare the peripheral and central nervous system (CNS) responsivities.This datase is part of the following. NCT04507126 - A Pilot Study of the Effects of Bacillus Calmette-Guérin (BCG) Immunization on Cerebrospinal Fluid and Blood-based Biomarkers in Older Adults - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04507126 NCT05004688 - A Trial to Evaluate the Effects of BCG in Adults With MCI and Mild-to-Moderate AD - - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT05004688

overall_design: Briefly, In the present study, Cerebrospinal Fluid (CSF) Cells were collected and cryopreseved from four subjects before (Baseline, BL) and after (3months and 1year) BCG Vaccination. The cells at each of the time points (i.e. BL, 3mo and 1yr) were stimulated with either X-Vivo i.e. control media, or lipopolysaccharide (LPS, 10ng/mL) or heat killed bacillus calmette guerin (HK-BCG, 1e5 cfu/mL) for four hours, immediately followed by  scRNA-seq on 10x. Additionally, peripheral blood mononuclear cells (PBMCs) from three subjects (Paired subjects to the CSF Cell samples)) before (Baseline, BL) and after (3months and 1year) BCG Vaccination were also stimulated with the same conditions followed by scRNA-seq using 10X.

first: Marc

middle: S

last: Weinberg

first: Steven

middle: E

last: Arnold


title: Degradation of AGO2 by TRIM25 drives cancer progression and chemotherapy resistance

status: Public on Apr 25 2026

city: 上海市

first: Jianxiu

last: Yu

state: 上海市

address: Room 202, Building 7, 280 South Chongqing Road,

department: Department of Biochemistry and Molecular Cell Biology

country: China

institute: Shanghai Jiao Tong University School of Medicine

type: Non-coding RNA profiling by high throughput sequencing

summary: AGO2, as a key member of the RISC complex, is underexpressed in a variety of tumor cells. It is shown that the E3 ligase TRIM25 is highly expressed in a variety of tumor cells and mediates the degradation of the ubiquitin-proteasome pathway of AGO2. This effect of TRIM25 on AGO2 promotes tumor progression and resistance of tumor cells to chemotherapeutic agents. The specific mechanism is that TRIM25 regulates the level of miR-148b-5p in cells through AGO2, and then regulates the downstream ABCC1. Based on the above results, targeting miR-148b-5p provides a new strategy for the treatment of tumors.

overall_design: mRNA expression profiles and miRNA expression profiles in H1299 stable cell lines

first: Zihan

last: Zhou


title: CNOT3 maintains ILC2 integrity by destabilizing Tbx21 and Rorc mRNAs [RNA-seq]

city: Akita

first: Megumi

last: Tatematsu

department: Department of Medical Biology

country: Japan

institute: Akita University Graduate School of Medicine

summary: Immune responses are initiated by activation of innate lymphoid cells (ILCs), T-bet-dependent natural killer and ILC1 cells, GATA-3-dependent ILC2 cells, and RORγt-dependent ILC3 cells. Despite accumulated knowledge of translational regulation in ILCs, comprehensive impact of mRNA decay on ILCs has not been clarified yet. CNOT3 is a main subunit of the CCR4-NOT complex which mainly destabilizes mRNAs by poly (A) deadenylation in eukaryotes. Here, we showed that CNOT3 is required for cell survival of all ILCs and that the absence of CNOT3 promoted T-bet and RORγt expression due to increased stability of Tbx21 and Rorc mRNAs in ILC2 cells and enabled them to produce granzyme B and IL-22. Likewise, Th1 and Th17 skewing was induced in CD4 T cells lacking CNOT3. Furthermore, CNOT3 in each ILC subset contributes to their type-specific immune responses. Thus, the CCR4-NOT complex controls ILC differentiation by inhibiting the potential for type 1 and 3 immunity.

overall_design:
To investigate roles of CCR4-NOT complex in ILCs, we compared expression profile of NK cells, ILC2s and ILC3s from  control and Cnot3 conditional KO mice.
RNA-seq data of spleen NK cells from Cnot3f/f mice and Cnot3f/f Il7r-Cre mice (biological triplicates). RNA-seq data of lung ILC2s from Cnot3f/f mice and  Cnot3f/f Il7r-Cre mice (biological triplicates). RNA-seq data of small intestine ILC2s from Cnot3f/f mice and Cnot3f/f Il7r-Cre mice (biological triplicates). RNA-seq data of small intestine CCR6+ ILC3s from Cnot3f/f mice and  Cnot3f/f Il7r-Cre mice (biological triplicates).


title: CNOT3 maintains ILC2 integrity by destabilizing Tbx21 and Rorc mRNAs [RIP-seq]

overall_design:
RIP-sequence was performed using anti-Cnot3 antibody to distinguish direct target mRNAs of CCR4-NOT complex in ILC subsets.
RIP-seq data of spleen NK cells for bindings of Cnot3 (bilogical triplicates).RIP-seq data of lung ILC2s for bindings of Cnot3 (bilogical duplicates). RIP-seq data of small intestine ILC2s for bindings of Cnot3 (bilogical duplicates). RIP-seq data of small intestine ILC3s for bindings of Cnot3 (bilogical duplicates).


title: The homozygous founder Psmb8 variant of Nakajo-Nishimura syndrome/proteasome-associated autoinflammatory syndrome causes panniculitis-associated lipoatrophy and a shortened lifespan in mice

status: Public on Apr 24 2026

city: Suita

first: Daisuke

last: Motooka

state: Osaka

address: 3-1, Yamadaoka

institute: NGS core facility, Research Institute for Microbial Diseases, Osaka University

summary: Nakajo-Nishimura syndrome/proteasome-associated autoinflammatory syndrome (NNS/PRAAS) is a hereditary autoinflammatory disease. Clinically, NNS/PRAAS is characterized by periodic fever, skin rash, partial lipo-muscular atrophy, and joint contractures. Among PRAAS, NNS, is genetically characterized by a homozygous founder variant in the proteasome subunit beta type 8 (PSMB8) gene encoding an inducible proteasome component β5i. To establish an in vivo animal model recapitulating NNS/PRAAS , we generated mice harboring this founder variant. In Psmb8G201V/G201V mice, the immature β5i subunit was increased and 20S proteasome activity was significantly reduced in the spleen, whereas 26S proteasome activity was preserved and ubiquitin accumulation was not apparent. Compared with wild-type mice,　Psmb8G201V/G201V mice exhibited a shortened lifespan and, as they aged, showed less weight gain and adipocyte shrinkage with interstitial macrophage infiltration and cytokine production/activation. The mutant mice also manifested significantly lower proportion of T cells in total splenocytes, with higher CD4+ and lower CD8+ T cell proportions. Psmb8G201V/G201V mice shared some characteristic autoinflammatory and progeroid phenotypes as observed in NNS/PRAAS patients, although their proteasome defect pattern was distinct. Thus, Psmb8G201V/G201V mice should be useful not only for investigation of NNS/PRAAS pathogenesis but also for examining the clinical effect of candidate drugs on NNS/PRAAS and related diseases.

overall_design: comprehensive analysis of deregulated genes in B cells, T cells or Non-BT cells from Psmb8 +/+ or G201V/G201V mice

first: Tomoyuki

last: Hara

first: Akira

last: Kinoshita

first: Jun

last: Hamazaki

first: Hiroaki

last: Hemmi

first: Takashi

last: Kato

first: Izumi

last: Sasaki

first: Yutaka

last: Inaba

first: Yusuke

last: Yamashita

last: Okuzaki

first: Koh-Ichiro

last: Yoshiura

first: Shigeo

last: Murata

first: Masatoshi

last: Jinnin

first: Tsuneyasu

last: Kaisho

first: Nobuo

last: Kanazawa


title: Transcription factor binding in early pancreatic progenitors (PP1)

city: New York

first: Wilfred

last: Wong

state: NY

address: 430 E 67th St

institute: Memorial Sloan Kettering Cancer Center

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We established a human pluripotent stem cell (hPSC)-derived pancreatic progenitor organoid (PO) culture that provides the cellular plasticity for PDAC modeling and supports robust gene editing. Through the combinatorial expression of oncogenic KRAS and deletion of multiple tumor suppressor genes (TSGs)，we successfully recapitulated the transcriptional hallmarks of initial malignant transformation and progression of PDAC in POs in vitro. Moreover, these POs exhibited distinct histopathology from preneoplastic pancreatic intraepithelial neoplasia (PanIN) and moderately differentiated to poorly differentiated PDAC upon orthotopic transplantation. Further chromatin accessibility profiling unveiled 1) a progressive loss of pancreatic lineage program during disease development, accompanied by repression of TET1, 5hmc marking and hypermethylation of essential pancreatic lineage transcription factors and 2) an emergence of trans-lineage/malignant feature, associated with the opening of AP-1 motif enriched chromatin regions. Gene perturbation screening identified FOSL2, FOS, and JUNB as pro-malignancy AP-1 factors during malignant transformation of POs. Notably, inhibition of ERK, a regulator of AP-1, not only reversed AP-1 levels and malignant feature in transformed POs, but also derepressed TET1 and its associated chromatin regions. Thus, our de novo PDAC POs faithfully model the disease development and reveal distinct but concerted mechanisms that drive the cellular plasticity in PDAC. The comprehensive validation of this model against clinical datasets approves its potential for discovery of therapeutic targets and biomarkers for preventive screening in the future.

overall_design: Examination of duplicates of early pancreatic progenitor using ChIP-seq

first: Xian

last: Zhang

first: Dapeng

last: Yang

first: Christina

last: Leslie

first: Danwei

last: Huangfu


title: Ngn3 reprograms late retinal progenitor cells through transcriptional and epigenetic mechnisms [ATAC-Seq]

city: Guangzhou

first: SHUYI

last: CHEN

state: Guangdong

address: 54 S. Xianlie Rd

department: State Key Laboratory of Ophthalmology

institute: Zhongshan Ophthalmic Center, SYSU

summary: Ngn family transcription factors exhibit potent capacity to promote neurogenesis under diverse cellular context. Using in vivo electroporation on newbone mouse pups retinas, we demonstrate that overexpression of Ngn3 (Ngn3-OE) reprogramms the differentiation competent status of late retinal progenitor celle (RPC), promoting rod photoreceptor differentiation while repressing the fates of Müller glial cell and other interneurons. Herein, we perform RNA-seq and ATAC-seq to investigate the underlying molecular mechanism by which Ngn3 reprogramms late RPCs.

overall_design: Ngn3-overexpressing plasmids were introduced into late-stage RPCs via in vivo electroporation in postnatal day 1 (P1) mouse pups. Following electroporation, GFP-labeled electroporated late RPCs were isolated using fluorescence-activated cell sorting (FACS). Isolated cells were then processes for RNA-seq and ATAC-seq.

first: Shuyi

last: Chen


title: Ngn3 reprograms late retinal progenitor cells through transcriptional and epigenetic mechnisms [RNA-Seq]


title: Chromatin Landscape Analysis of Patient PDAC

overall_design: Examination of nuclei from frozen sections of patient PDAC samples

first: Adrien

last: Grimont

first: Victoria

middle: G

last: Aveson

first: Rohit

last: Chandwani

first: Steven

middle: D

last: Leach


title: Chromatin landscape analysis of pancreatic progenitor organoids (POs) bearing PDAC related mutations [ATAC]

overall_design: Examination of duplicates per genotype of POs in in vitro culture


title: Transcriptome analysis of pancreatic progenitor organoids  (POs) carrying PDAC related mutations, treated with ERK inhibitors and depleted of AP-1 factors

overall_design: Triplicates of PO samples genetically modified and duplicates of PO samples treated with ERK inhibitors were examined.


title: Transcriptional and immune repertoire profiling of mismatch repair-deficient colorectal cancer

status: Public on Apr 23 2026

city: Southampton

first: Stephen

middle: Mark

last: Thirdborough

state: Hants

address: Tremona Road

department: School of Cancer Sciences

country: United Kingdom

institute: University of Southampton

summary: Colorectal cancers (CRC) with deficient mismatch repair (dMMR) exhibit variable responses to immune checkpoint inhibitors, despite their immunogenic nature. To investigate the molecular basis of this heterogeneity, we performed integrated bulk RNA sequencing and immune repertoire profiling on tumor and adjacent normal mucosa from treatment-naïve dMMR CRC patients. Using weighted gene co-expression network analysis, we identified transcriptional modules associated with T and B cell clonality, immune-metabolic interactions, and therapeutic responsiveness. Our dataset provides a valuable resource for understanding the tumor microenvironment in dMMR CRC and supports the development of biomarkers for patient stratification beyond mismatch repair status.

overall_design: Bulk RNA-sequencing of dMMR CRC tumors (n=30) and immune repertoire sequencing (TRB and IGH) of matched tumor and normal adjacent mucosa.

middle: M

first: Sheah Lin

last: Lee


title: PDS5 proteins control genome architecture by limiting the lifetime of cohesin-NIPBL complexes [Hi-C]

status: Public on Apr 22 2026

city: Vienna

first: Roman

middle: R

last: Stocsits

address: Campus-Vienna-Biocenter 1

country: Austria

institute: IMP - Research Institute of Molecular Pathology

summary: Cohesin-NIPBL complexes extrude genomic DNA into loops that are constrained by CTCF boundaries. This process has important regulatory functions and weakens the separation between euchromatic and heterochromatic compartments. Cohesin can also bind PDS5A or PDS5B, which do not support loop extrusion but are required for the formation of CTCF boundaries. How PDS5 proteins perform this function is unknown. Here we show by in vitro single-molecule imaging that PDS5 proteins stop loop extrusion by facilitating the dissociation of NIPBL from cohesin. Hi-C experiments suggest that this function is required for the establishment of CTCF boundaries in cells. In silico modelling indicates that PDS5 proteins enable the separation between compartments by limiting cohesin’s velocity and chromatin-residence time. The degree of this compartmentalization depends on the frequency with which chromatin is extruded relative to the time it takes for compartments to form. These results identify PDS5 proteins as key regulators of genome organization.

sample_organism:
Gallus gallus
Homo sapiens

platform_organism:
Gallus gallus
Homo sapiens

overall_design: Hi-C to analyze the effect of mutations on chromatin architectures in different conditions

first: Gordana

last: Wutz

first: Jan-Michael

last: Peters

first: Wen

last: Tang


title: Male voles Arvicola terrestris scherman escaping to seasonal breeding: an example of a disturbance likely induced by environmental change

city: clermont ferrand

first: yoan

last: renaud

address: place henri dunand

country: France

institute: igred

summary: The work was initiated to characterize the testicular gene expression profile of winter and summer males to better understand the physiological changes of these seasonnal breeders. It revealed that a subpopulation of males did not have a seasonnal behavior and were active during the winter, however with a particular gene expression profile. These males may be at the origin of the spring peaks of reproduction, causing outbreaks of the vole populations. We hypothesize that climate change, offering warmer winters and better acces to food supply may at the origin of the dysregulation of the circannual biological clocks of these pest rodents.

overall_design: RNAs were extracted from testis of wild Arvicola terrestris males captured in winter or summer. RNAseq analysis was performed and the two groups were compared.

first: Fabrice

last: SAEZ

first: Yoan

last: RENAUD


title: Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 to establish T cell niches

city: Epalinges

first: Nagham

last: Alouche

address: Chemin des Boveresses 155

department: Immunobiology

country: Switzerland

institute: University of Lausanne

summary: Secondary lymphoid organs are structurally organized by fibroblastic reticular cells (FRCs), which coordinate immune cell positioning and support adaptive immune responses. However, the mechanisms underlying the differentiation of FRCs into distinct functional subsets remain poorly understood. To investigate the role of Notch2 signaling in this process, we performed single-cell RNA sequencing (10x Genomics) on lymph node immune cells from mice lacking Notch2 expression specifically in FRCs. Our dataset reveals how Notch2 signaling shapes FRC subset differentiation and modulates the composition of neighboring immune cell populations.

overall_design: Lymph node immune cells from two Notch2^fl/fl^ mice and two Ccl19-Cre × Notch2^fl/fl^ mice, all on a C57BL/6 background, were processed for scRNA-seq. Live immune cells were sorted using a MoFlo Astrios EQ cell sorter, with the following final proportions: 20% CD45⁺ CD19⁺, 20% CD45⁺ CD3e⁺, 30% CD45⁺ CD19⁻ CD3e⁻ CD11c⁺ MHCII^hi^, and 30% CD45⁺ CD19⁻ CD3e⁻ CD11c⁻ MHCII^low^

first: Corinne

last: Peter

first: Giovanna

last: Ambrosini

first: Karolina

last: Bojkowska

first: Julien

last: Marquis


title: PDS5 proteins control genome architecture by limiting the lifetime of cohesin-NIPBL complexes [ChIP-Seq]

overall_design: The objective of this experiment was to investigate the role of cohesin and CTCF in positioning in different depletion conditions.


summary: Secondary lymphoid organs are structurally organized by fibroblastic reticular cells (FRCs), which support immune cell positioning and adaptive immune responses. However, the mechanisms driving the differentiation of FRCs into distinct functional subsets remain unclear. To investigate the role of Notch2 signaling in this process, we performed single-cell RNA sequencing (10x Genomics) on lymph node FRCs lacking Notch2 expression. Our dataset highlights how this pathway contributes to FRC differentiation.

overall_design: Two experimental batches were performed. The first batch included single-cell RNA sequencing (scRNA-seq) analysis of lymph node fibroblastic reticular cells (FRCs) from Ccl19-Cre x R26R-EYFP mice and non-littermate Ccl19-Cre x Notch2^fl/fl x R26R-EYFP mice, both on a C57BL/6 background. The second batch included Notch2^fl/fl control mice and their littermate Ccl19-Cre x Notch2^fl/fl mice, also on a C57BL/6 background.

first: Isabelle

last: Dupanloup


summary: Secondary lymphoid organs are organized by fibroblastic reticular cells (FRCs), which direct immune cell positioning and support adaptive immunity. However, the mechanisms driving FRC subset differentiation remain unclear. To uncover signaling pathways involved in this process, we performed ATAC-seq on lymph node FRCs lacking Notch2. Our data reveal chromatin remodeling changes in the absence of Notch signaling.

overall_design: We performed ATAC-seq analysis on fibroblastic reticular cells (FRCs) isolated from brachial, axillary and inguinal lymph nodes of Ccl19-Cre x Notch2^fl/fl mice and their Notch2^fl/fl littermate controls, all on a C57BL/6 background.

first: Allison

last: Burns


title: Identification of two genes associated with recurrence in Paget’s disease and construction of a predictive model

status: Public on Apr 21 2026

city: Fuzhou

first: Pengfei

last: Cha

address: 243xihong road

institute: Fuzhou Dermatology Hospital

summary: In summary, RNA‑seq analysis revealed distinct functional profiles between MPD and EMPD, with recurrence in MPD associated with developmental and differentiation pathways, while EMPD recurrence was linked to immune and inflammatory processes. Using WGCNA, we identified KLF13 and TIA1 as hub genes, which were subsequently validated as independent prognostic biomarkers in internal and external datasets. A risk‑score model based on these genes effectively stratified patients by outcome. Further studies are needed to elucidate the detailed molecular mechanisms underlying their roles in PD progression and recurrence.

overall_design:
A total of 11 patients with EMPD and 28 patients with MPD were enrolled in this study.All participants provided written informed consent voluntarily. Inclusion criteria were: (1) primary tumor resection with R0 margins and no prior treatment; (2) pathological confirmation of Paget cells within the tumor; (3) age between 18 and 80 years; and (4) EMPD tumor originating from the perineal region, specifically the external genitalia, anus, and perineal skin. Patients were excluded if they: (1) had a history of or concurrent other malignancies, or (2) presented with distant metastasis at diagnosis.

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title: Cell-type specific translated mRNA expression in the denervated cervical cord after stroke.

status: Public on Apr 20 2026

city: Niigata-shi

first: Tokiharu

last: Sato

state: Niigata

address: 1-757 Asahimachidori, Chuo-ku

department: Department of System Pathology for Neurological Disorders

institute: Niigata University, Brain Research Institute

summary: mRNA expressions during the process of reorganization of the corticospinal tract after stroke were examined by RiboTag-RNA-seq in V2a spinal interneurons, astrocytes, and microglia in the denervated cervical cord.

overall_design: RiboTag-RNA-seq was performed with samples of the cervical cord on the denervated side, collected for controls and day 3, 7, 14, and 28 after stroke in Chx10-Cre;RiboTag, Aldh1l1-CreER;RiboTag and Cx3cr1-CreER;RiboTag mice, and 2, 4, and 8 h after rotarod training on day 14 after stroke in Chx10-Cre;RiboTag and Aldh1l1-CreER;RiboTag mice (n = 3 per group).

first: Masaki

last: Ueno

first: Masato

last: Yano


title: Coordinated regulation of calcium homeostasis and pathogenicity by a dual-action transcriptional regulator Cas5 [RNA-Seq]

status: Public on Apr 18 2026

city: Shanghai

first: JIHONG

last: liu

state: Shanghai

address: No. 320 Yueyang Road, Shanghai

institute: siii

summary: As a clinically relevant opportunistic human fungal pathogen, C. albicans is able to rapidly sense and adapt to changing microenvironments within the host, a process that is essential for its successful invasion and survival. Although studies have shown that the transcription factor Crz1 is the master regulator of calcium (Ca2+) homeostasis, accumulating evidence supports a clear involvement of other participants in this biological process. Here, following a high-throughput genetic screen, we identified the transcription factor Cas5 as a novel positive regulator of Ca2+ homeostasis in C. albicans. Mechanistically, Cas5 modulates Crz1 dephosphorylation, nuclear localization and Crz1-dependent signaling pathway by inhibiting protein kinase Tpk1 to maintain Ca2+ homeostasis. Furthermore, our study confirms that the calcineurin-mediated virulence is dependent on transcription factor Cas5 in a Crz1-independent manner, complementing a long-standing knowledge gap in the regulation of virulence by calcineurin. Taken together, our findings elucidate that a dual-action transcriptional regulator Cas5 coordinates both Ca2+ homeostasis and pathogenicity of C. albicans in the host.

overall_design: Overnight culture of WT, cnb1Δ/Δ, crz1Δ/Δ and cas5Δ/Δ strains in YPD, the next day, Cell pellets were transfer to fresh YPD for the starting concentration of C. albicans OD600 is 0.1 and culture to the logarithmic phase of growth at 30 ℃; where the calcium ion treatment group is to add 0.2 M calcium and continue to incubate for 1 h. Each strain was cultured in three independent parallel groups for each condition at the same time. Take 2 OD C. albicans to remove the supernatant by rapid centrifugation at 4 ℃, frozen in liquid nitrogen, and then use the above total RNA extraction method for RNA extraction, extraction of RNA samples using 1.5% agarose gel electrophoresis identification. The total RNA samples were sent to Tianjin Novogene for quality control, and the subsequent sequencing of the samples was carried out. The final library construction and Illumina HiSeq2000 sequencing of the samples were done by Tianjin Novogene.


title: Differentiating naturally occurring and disease associated autoantibodies in MPO-ANCA vasculitis through immunogenomic and epitope comparisons

status: Public on Apr 17 2026

city: Chapel Hill

first: Office of Genomics Research

last: UNC Lineberger Comprehensive Cancer Center

state: NC

address: 125 Mason Farm Road, CB #7599 5105-5106 Marsico Hall

institute: University of North Carolina at Chapel Hill

summary: It has been established that there are naturally occurring autoantibodies including ANCAs that are found in healthy individuals. While ANCAs are pathogenic in patients with vasculitis, they can be present without active clinical disease. This raises the question of what is distinct about the autoantibodies which cause disease. We used highly sensitive methods to isolate autoantibody producing cells from healthy individuals and patients with MPO-ANCA to sequence the BCRs (autoantibodies). We also used serum samples to analyze the reactive epitopes from both groups. We found that the isolated autoantigen specific B cells from our patients (but not healthy individuals) produced high levels of detectable MPO-ANCAs. The BCRs from patient cells showed clonal expansion and significant overlap in the complementarity determining region 3 (CDR3). We also identified distinct epitopes bound by patient autoantibodies only. Our study highlights the differences in naturally occurring autoantibodies (from healthy individuals) compared to autoantibodies identified in patients with MPO-ANCA.

overall_design: Cryopreserved peripheral blood mononuclear cells (PBMCs) from patients and healthy individuals collected with consent were thawed and labeled with antigen specific tetramers to isolate antigen specifi B cells, the remaining cells were also collected. Additional subpopulation of B cells was isolated from the same individuals. Cells were cultured and collected for total BCR sequencing.

first: Dhruti

middle: P

last: Chen

first: Mark

last: Woodcock

first: Benjamin

last: Vincent

first: Donna

middle: O

last: Bunch


title: Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1

city: Martinsried

first: Assa

last: Yeroslaviz

state: Bavaria

address: Am Klopferspitz 18

department: computational Biology

country: Germany

institute: Max-Planck-Institute for biochemistry

summary: Regulation of metabolic enzymes through degradation by the ubiquitin-proteosome system regulation is essential towards maintenance of cellular homeostasis. Our approach directly addresses a problem in the field; linking metabolic signal to an E3 ligase response. We employ active E3 ligase profiling coupled with broad MS-based screening, to reveal the changes in the proteome and E3 ligase-ome in response to the starvation or excess of a specific metabolite. We then use computationally driven strategies to connect these responses before in vitro and in cellulo reconstitution. The application of this strategy on cysteine metabolism led to our finding of LRRC58 mediated control of CDO1 degradation. Through reconstitution of this system, we also reveal that endogenous CDO1 degradation by LRRC58 is distinct from degradation induced by a molecular glue. Additionally, we have visualized CDO1 ubiquitylation by an LRRC58 CRL through cryo-EM, demonstrating the structural basis for CDO1 targeting by LRRC58.

overall_design: RNA-Seq was performed for HEK293T cells grown for 24hr in either normal media or Cys-free media


title: IL-9 and Blimp-1 protect the transcriptional identity of group 2 innate lymphocytes in allergic asthma

city: Pittsburgh

first: Amanda

middle: Catherine

last: Poholek

state: Pennsylvania

address: 4401 Penn Ave., Rangos Research Center 8129

department: Pediatrics

institute: University of Pittsburgh

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

overall_design: Refer to individual Series


title: Gestational and Postnatal Age Define Airway Epithelial Maturation and RSV Responses During the First Year of Life: Results of an ex-vivo/in-vitro Airway Epithelial Cell Study

city: Belfast

first: Guillermo

last: López-Campos

state: Northern Ireland

address: 97 Lisburn road

department: Welcome-Wolfson Institute for Experimental Medicine

institute: Queen's University of Belfast

summary: Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants globally.  Newborns, especially those born prematurely, are at increased risk of severe RSV-related illness, yet the influence of age on early-life airway epithelium innate immune responses remains relatively understudied.  We established ex-vivo/in-vitro well-differentiated paediatric nasal epithelial cell (WD-PNEC) cultures derived from preterm and term infants at birth and again at one-year-old.  Infection characteristics and innate immune responses were determined following in vitro RSV infection.  RSV growth kinetics and cytopathology were similar irrespective of gestation or age.  Secretion of interferon lambda-1 (IFN-λ1), CXCL10, CCL5, and CXCL8 were comparable between RSV-infected preterm- and term-newborn WD-PNECs.  Importantly, following RSV infection, secretion of RSV-induced IFN-λ1 (p<0.05) and CCL5 (p<0.01) and expression of the IFN-stimulated gene, IFI6 (p<0.05) were significantly higher in one-year- compared to newborn-derived WD-PNECs. Interestingly, secretion of the cell signalling cytokine pleiotrophin increased significantly with longer gestation (p<0.01) and older age (p<0.001). Differential gene expression analysis demonstrated 156 differentially expressed genes (DEGs) with age and revealed transcriptomic changes linked to gestation in newborns that persisted at 1-year. These findings indicate two major conclusions.  Firstly, we report transcriptomic differences in airway epithelial cell (AEC) development between term and preterm infants across the first year of life.  Secondly, we demonstrate that RSV infection responses of AECs become more robust with age in early-life.  Further investigation of identified DEGs and differentially expressed chemokines/cytokines is warranted to clarify their role in increased susceptibility of very young infants to severe RSV disease, as well as the significance of these factors in the emergence of wheezing phenotypes and long-term respiratory outcomes.

overall_design: Well-differentiated primary nasal epithelial cells from newborn and 1 year old infants were mock-infected and infected with RSV BT2a and gene expression was measured at 96 hpi.

first: Helen

last: Groves

first: Mary

last: McCabe

first: Jonathon

last: Coey

first: Lindsay

last: Broadbent

first: Hong

last: Guo-Parke

last: Lopez Campos

first: Michael

last: Shields

first: Ultan

middle: F

last: Power


title: Changes in tRNA wobble modifications under a norepinephrine gradient coincide with codon-biased translation and induction of virulence in EHEC O157:H7

city: Cambridge

first: Abigail

last: McShane

address: 77 Massachusetts Ave

department: Biological Engineering

institute: Massachusetts Institute of Technology

summary: The goal of this study was to investigate how Enterohemorrhagic Escherichia coli O157:H7 (EHEC) strain EDL933 remodels its tRNA pool in response to the catecholamine hormone norepinephrine, a host-derived cue that stimulates virulence in this pathogen. Here, we performed Absolute Quantitative RNA-sequencing (AQRNA-seq) to measure levels of tRNA isoacceptors in EHEC samples exposed to 0, 25, and 50 micromolar norepinephrine.

overall_design: An overnight culture of EHEC O157:H7 EDL933 was diluted 1:100 in DMEM low glucose (supplemented with HEPES and pyruvate, no serum) with 0, 25, and 50 micromolar norepinephrine. cDNA libraries were constructed from purified small RNA using a variation of the Absolute Quantitative RNA Sequencing (AQRNA-seq) library preparation protocol (PMCID: PMC8355021), described in the library construction protocol. Constructed libraries were subjected to quality assessment using Fragment Analyzer and qPCR, followed by paired-end sequencing (PE75) on a Illumina MiSeq platform.

first: Peter

last: Dedon


title: BMP signaling regulates dorsal skeletal growth in the sea urchin embryo

status: Public on Apr 16 2026

first: William

middle: Brent

last: Douglas

state: PENNSYLVANIA

address: 6336 Aurelia St., 1

department: Biological Sciences

institute: Carnegie Mellon University

summary: The development of the elaborate, calcified endoskeleton of sea urchin embryos is a model for understanding the dynamic nature of developmental gene regulatory networks and the control of biomineralization. While several signaling pathways have been shown to regulate  gene expression and biomineral formation by sea urchin skeletogenic cells, important gaps in our understanding remain. Here, we focused on signals regulate skeletogenesis along the dorsal/ventral axis of the late-stage embryo. We used specific inhibitor of Type I BMP receptors, K02288, to show that BMP signaling regulates skeletal growth selectively in the dorsal region. K02288 treatment led to dorsal skeletal defects and inhibited the expression of genes typically expressed specifically in the dorsal skeletogenic cells, including biomineralization genes. Using RNA-seq, we identified genes that were uniquely downstream of either the BMP or a ventral signaling pathway (the VEGF pathway) at late developmental stages and genes downstream of both pathways. Our findings establish BMP signaling as a key pathway regulating dorsal skeleton formation and show that BMP signaling functions in concert with VEGF signaling to define the dorsal/ventral axis of the skeleton.

overall_design: To understand the separate contributions of VEGF signaling and BMP signaling to late-stage sea urchin embryonic skeletogenesis, Lytechinus variegatus embryos were cultured until after the formation of the tri-radiate spicule rudiments (~18-20hpf @ 21oC) at which point embryos were incubated in various treatment conditions (DMSO in ASW, 75 nM axitinib in ASW, or 1 μM K02288 in ASW). Embryos were then cultured until the late pluteus stage (2dpf @ 21oC). Embryos were lysed and total RNA was extracted using a Pure Link™ RNA Mini Kit (Invitrogen) following the manufacturer's protocol. Samples were then treated with Turbo DNase™ (Invitrogen) and LiCl precipitated to remove genomic DNA. RNA samples were then shipped to Novogene Corporation Inc. for sequencing. mRNA was purified by Novogene using poly-A enrichment purification, strand-specific cDNA synthesis was performed, and sequenced by synthesis using the Illumina sequencing platform.

middle: B

first: Charles

middle: A

last: Ettensohn


title: Variant U1 snRNAs contribute to cell cycle and differentiation control of human iPS cells

status: Public on Apr 15 2026

city: Göttingen

first: Argyris

last: Papantonis

address: Robert-Koch-Str. 40

department: Institute of Pathology

institute: University Medical Center Göttingen

summary: Maintenance of stem cell identity as well as differentiation of stem cells into the various lineages requires intricate regulation of gene expression. Despite intensive research, our understanding of these regulatory networks remains incomplete. Here, we focus on the understudied paralogs of the U1 small nuclear RNA (snRNA) gene known as variant U1 (vU1) snRNAs. By generating isogenic knockout lines of human induced pluripotent stem cells for two different vU1s, we show that their loss profoundly changes both hiPSC gene expression and cell cycle profiles. These changes appear to manifest at the level of alternative splicing choices, including those at recursive splicing sites, and lead to the differential availability of stem cell regulators. Together, our results shed new light on the function of vU1 snRNAs and further our understanding of the programs controlling human pluripotency.

overall_design: We generated the two CRISPR-knockout hiPSc lines of vU1.3 and vU1.8 snRNA genes, sequenced their transcriptomes, and quantified differential gene expression, alternative and recursive splicing. We also immunoprecipitated RNAs interacting with either the vU1.8 or the vU1.3 snRNA (stabilised via crosslinking), followed by total RNA-seq.

first: Yajie

last: Zhu

first: Konstantinos

last: Sofiadis


title: Neurotranscriptomics of mutualistic cleaning in Ladridae wrasses

city: Austin

first: Rebecca

middle: L

last: Young

state: TX

address: 2415 Speedway #C0930, Patterson Lab 607A

institute: University of Texas at Austin

summary: Despite the astonishing diversity of life, evolutionary biologists have documented numerous instances where species converge in how they behave, look, and function. Given the importance of happenstance in evolution, it is often assumed that mechanisms driving independent evolution of similar phenotypes (convergence) are distinct; yet recent discoveries suggest that conserved genomic mechanisms can underlie convergent traits. Here, we generate forebrain transcriptomes from six sympatric Labridae wrasses that vary in mutualistic cleaning behavior and apply differential gene expression, co-expression, and phylogenetic comparative analyses to address three questions. First, do neurotranscriptomes vary among species with distinct cleaning behavior? Second, do species that have independently evolved facultative cleaning share neurotranscriptomic patterns? Third, are transcriptomic signatures linked to facultative cleaning also expressed in obligate cleaners? We identify shared neurotranscriptomic patterns in the repeated evolution of facultative cleaning, including 25 novel candidate genes. We then find that transcriptomic patterns associated with facultative cleaning are shared in our focal obligate cleaner species, with more genes than expected by chance with concordant expression patterns in obligate and facultative cleaners. Our results illuminate the neuromolecular basis of cooperative behavior and demonstrate the predictive potential of comparative transcriptomics to unravel the mechanistic underpinnings of the repeated evolution of complex phenotypes.

sample_organism:
Halichoeres melanurus
Thalassoma lunare
Coris batuensis
Hemigymnus melapterus
Labrichthys unilineatus

overall_design: Transcriptome profiling of a forebrain section taken from five species of Labridae wrasses (Hemigymnus melapterus, Coris batuensis, Thalassoma lunare, Halichoeres melanurus, Labrichthys unilineatus) using 3'tag-seq.

first: Hans

last: Hofmann

first: Redouan

last: Bshary

first: Chelsea

last: Weitekamp

first: Zegni

last: Triki

first: Yiheng

last: Su

last: Beman

first: Matthew

last: Petershack


title: Inference of emergent spatio-temporal processes from single-cell sequencing reveals feedback between de novo DNA methylation and chromatin condensates [Bisulfite-Seq 2]

status: Public on Apr 14 2026

first: Laura

last: Biggins

address: Babraham Research Campus

department: Bioinformatics

institute: The Babraham Institute

type: Methylation profiling by high throughput sequencing

summary: Recent breakthroughs in single-cell genomics allow probing molecular states of cells with unprecedented detail along the sequence of the DNA. Biological function relies, however, on emergent processes in the three-dimensional space of the nucleus, such as droplet formation through phase separation. Here, we use single-cell multi-omics sequencing to develop a theoretical framework to rigorously map epigenome profiling along the DNA sequence onto a description of the emergent spatial dynamics in the nucleus. Drawing on scNMT-seq multi-omics sequencing in vitro and in vivo we exemplify our approach in the context of exit from pluripotency and global de novo methylation of the genome. We show how DNA methylation patterns of the embryonic genome are established through the interplay between spatially correlated DNA methylation and topological changes to the DNA. This feedback leads to the predicted formation of 30-40nm sized condensates of methylated DNA and determines genome-scale DNA methylation rates. We verify these findings with orthogonal single cell multi-omics data that combine the methylome with HiC measurements. Notably, this scale of chromatin organization has recently been described by super-resolution microscopy. Using this framework, we identify local methylation correlations in gene bodies that precede transcriptional changes at the exit from pluripotency. Our work provides a general framework of how mechanistic insights into emergent processes underlying cell fate decisions can be gained by the combination of single-cell multi-omics and methods from theoretical physics that have not been applied in the context of genomics before.

overall_design: E14 mESC were cultured in 2i+LIF media. For induction for 2i-relase experiment, the cells were rinsed with PBS before the culture media was changed to serum + LIF medium. Each each collection time point cells were lysed and processed for BS-seq

first: Fabrizio

last: Olmeda

first: Tim

last: Lohoff

first: Ioannis

last: Kafetzopoulos

first: Stephen

last: J Clark

last: Benson

first: Fatima

last: Santos

first: Felix

last: Krueger

first: Simon

last: Walker

first: Wolf

last: Reik

first: Steffen

last: Rulands


title: Miniaturisation of duckweeds occurred through compression of the angiosperm body plan

city: Sutton Bonington

first: Alexander

middle: George

last: Ware

state: Leicestershire

address: Sutton Bonington Campus

institute: University of Nottingham

summary: We performed RNA-seq on microdissected regions of Lemna minor (clone 8623) and Spirodela polyrhiza (clone 9509) fronds, alongside the related aroids Pistia stratiotes (water lettuce) and Colocasia esculenta (taro), to define region-specific transcriptomes and compare organ-identity programmes across species. Transcript abundance was quantified with Salmon v1.10.0 and cross-species comparisons were performed on 6,230 one-to-one orthologues identified by OrthoFinder v3.0.1b1.

sample_organism:
Colocasia esculenta
Lemna minor
Pistia stratiotes
Spirodela polyrhiza

overall_design: RNA-seq of microdissected frond regions (Apical, Basal, LowerWall, NodeTract for duckweeds; plus Stipe, Node and Tract for Spirodela; Apical, Basal, Petiole, Sheath for taro; Apical, Basal, Petiole, Stem, Stolon for Pistia) with 2-6 biological replicates per region per species. 79 samples total (14 Lemna, 28 Spirodela, 20 Pistia, 17 Taro).

first: Anthony

last: Bishopp

first: Rahul

last: Bhosale

first: Emily

last: Chan


title: NEAT1-driven ceRNA network in multiple myeloma

city: MILAN

first: Luca

last: Agnelli

address: Venezian 1

department: Department of Advanced Diagnostics

country: Italy

institute: IRCCS Istituto Nazionale dei Tumori

summary: The lncRNA NEAT1 is overexpressed in multiple myeloma (MM) plasma cells and plays a key role in MM pathogenesis. NEAT1 is involved in ceRNA network in several cancers; however, data in MM are virtually absent. This study identified a NEAT1-driven ceRNA network involving 96 miRNAs and 40 target genes, selected as concurrently downregulated in NEAT1-KD AMO1 cells and upregulated in NEAT1-overexpressing AMO1 cells (AMO1-OVX). The co-expression of NEAT1 and the targets was validated in MM patients (GSE116294, GSE13591, GSE6477, CoMMpass), and in NEAT1-KD NCI-H929, LP1, and KMS27 cell lines, showing for all targets a consistent downregulation, resembling that of NEAT1. The functional implication of the ceRNA network was explored by functional enrichment analyses of the 40 targets, identifying 78 significant gene sets, 17 of which found significantly enriched by GSEA analysis in at least one experimental condition among NEAT1-KD LP1, NCI-H929, and KMS27 cells, AMO1-OVX cells, or the extreme quartiles of NEAT1 expression in the CoMMpass dataset. Noteworthy, the cell cycle gene set was validated in 5 out of 6 conditions tested, suggesting that in MM the impact of NEAT1 upregulation on the cell cycle, experimentally demonstrated in our earlier publications, may be attributable, at least partially, to ceRNA mechanisms.

overall_design: AMO1, LP1, and NCI-H929 human multiple myeloma cell lines were silenced for NEAT1 expression by the use of specific Gapmers. Global transcript expression was investigated by RNA sequencing analyses, comparing data from NEAT1-KD cell lines with the relative control condition (SCRgapmer) at 48 days.

first: Domenica

last: Ronchetti

first: Valentina

last: Traini

first: Ilaria

last: Silvestris

first: Giuseppina

last: Fabbiano

first: Andrea

last: Devecchi

first: Federica

last: Torricelli

first: Noemi

last: Puccio

last: Craparotta

first: Marco

last: Bolis

first: Roberto

last: Piva

first: Antonino

last: Neri

first: Francesco

last: Passamonti

first: Niccolò

last: Bolli

first: Elisa

last: Taiana


title: PD-1 Deficiency Exacerbates Mycobacterium abscessus Lung Infection via Metabolic Rewiring and Dysregulated Neutrophil  Responses

city: Chongqing

first: Xiaowen

last: Yu

address: No. 6, Panxi 7th Branch Road, Jiangbei District

department: Basic Research Laboratory of Traditional Chinese Medicine

institute: Chongqing Traditional Chinese Medicine Hospital

summary: A PD-1-deficient MAB-infected mouse model was established. The impact of PD-1on bacterial clearance, immune cell activity, and metabolism was evaluated via colony counting, histopathology, flow cytometry, multiplex immunofluorescence, transcriptomics, and metabolic profiling. PD-1−/− mice exhibited increased susceptibility to MAB. Late infection featured further Th1 decline, neutrophil rise, and enhanced glycolysis. Peripheral blood displayed lower CXCL9 but elevated IL-6, IL-21, IL-27, CXCL2, CXCL10, and S100A8 production.

overall_design: Transcriptomic Analysis of Immune Cell Recruitment and Functional Alterations in Pulmonary Tissues of Wild-Type and PD-1-Deficient Mice Following MAB Infection at 21 Days Post-Infection

first: Lu

last: Huang


title: Research on the Pathogenesis of Systemic Sclerosis

city: Hefei City

first: jing

last: wang

address: No. 81 Meishan Road

institute: Anhui Medical University

summary: By analyzing differentially expressed genes, a preliminary CeRNA network related to the pathogenesis of SSc was established. Further studies will be conducted to determine the impact of genes in this network on the development of SSc.

overall_design: RNA-seq and miRNA-seq were performed on five samples each from the systemic sclerosis case group and the healthy control group.

first: Jing

last: Wang


title: Limited Immune Perturbations in Mice Exposed to Sustained Low-Dose Ionizing Radiation

city: Ottawa

first: Seung-Hwan

last: Lee

state: Ontario

address: 451 Smyth Road

department: Biochemistry, Immunology and Microbiology

country: Canada

institute: University of Ottawa

summary: The effects of high-dose ionizing radiation (HDIR) exposure on the immune system are largely understood with consensus, yet there remains a fragmented understanding of the impact of low-dose ionizing radiation (LDIR) on immune homeostasis, especially in sustained exposure conditions. This study investigates the effects of continuous LDIR exposure on the murine immune system, focusing on transcriptomic responses and cellular perturbations following low-dose-rate whole-body 𝛾-radiation. Female 18-week-old C57BL/6 mice were continuously exposed to low-dose-rate 60Co radiation over a period of 7 days, resulting in cumulative absorbed doses of 10 mGy and 100 mGy. Our findings indicate that the LDIR exposure induced, at most, only minimal transcriptomic perturbations to the immune system in C57BL/6 mice. These results suggest a preservation of immune cell homeostasis under the sustained low-dose-rate exposure conditions studied. It contributes to a broader understanding of radiation biology, emphasizing that the effects of LDIR on the immune system can be limited at low-dose-rates in mice.

overall_design:
Eighteen-week-old female C57BL/6 mice (Jackson Laboratories) were housed and irradiated at the CNL (Chalk River, Ontario, Canada). Whole-body gamma irradiation was administered using a Nordion (Ottawa, Ontario, Canada) Gammabeam 150C irradiator equipped with a Cobalt-60 source. The irradiation was continuous for 7 days in the pathogen-free irradiation hall of the CNL. Treatment groups were positioned at varying distances from the irradiator to achieve different dose rate exposures. Mice receiving a cumulative dose of 10 mGy (n=6) received an average dose rate of 0.0614mGy/hr. Mice receiving a cumulative dose of 100 mGy (n=6) received an average dose rate of 0.625mGy/hr. The positioning ensured the beam targeted the mid-level of each cage, centered between the two cages. Dosimetry was performed using an Exradin A8 ion chamber and a Supermax electrometer. Control mice (n=6) were housed separately in a conventional animal room.
***Note: Raw FASTQ files for two samples (10 mGy biological replicates 1 and 5 (B1 & B6)) were irretrievably lost due to a storage system failure at the Digital Research Alliance of Canada HPC. Processed TPM values for these samples are retained in the submitted matrix and were generated prior to the data loss. Furtermore, Kallisto abuindances.tsv were retained and submitted for all files.

first: Bryan

last: Marr

first: Holly

last: Laakso

first: Melinda

last: Blimkie

first: Andrew

last: Cao

first: Abrar Ul Haq

last: Khan


title: eIF4G2-dependent translation restrains pancreatic cancer progression

status: Public on Apr 13 2026

city: New York

first: Chritine

last: Chio

department: ICG

institute: Columbia Unievristy

summary: Pancreatic ductal adenocarcinoma (PDA) is among the most lethal cancers, driven by cellular plasticity that fuels therapeutic resistance and early dissemination. The contribution of translational control to this plasticity remains poorly understood. Through an in vivo CRISPR/Cas9 screen, we identify the non-canonical initiation factor eIF4G2 (DAP5/NAT1) as a translational checkpoint restraining PDA progression. Loss of eIF4G2 accelerated tumor growth, induced poorly differentiated, basal-like histology, and triggered widespread metastatic spread. Ribosome profiling revealed that eIF4G2 loss did not increase bulk protein synthesis but instead suppressed translation of a selective regulon, including tumor suppressors such as PTEN and CREBBP. Functional studies confirmed that PTEN loss was sufficient to drive dedifferentiation but insufficient to promote metastasis, implicating the broader eIF4G2-dependent program—including translational control of transcriptional regulators like CREBBP—in limiting dissemination. Consistently, eIF4G2-deficient tumors showed transcriptomic enrichment of migratory and stemness programs. Computational inference from human PDA datasets demonstrated reduced eIF4G2 activity in metastases, aligning with basal-like features and predicting poorer survival. These results define eIF4G2 as a translational regulator that maintains epithelial identity and restrains metastatic potential, highlighting selective translation as a determinant of PDA subtype and clinical outcome.

overall_design: To define the selective translational program regulated by eIF4G2, we performed ribosome profiling (Ribo-seq) and RNA-seq in three independent murine PDA cell lines (ccmT1, ccmT2, and ccmT4) transduced with sgRosa or sgEif4g2

first: Justin

last: Powers

first: Wei

last: Lai

first: Hiroki

last: Kobayashi

first: Pardis

last: Ahmadi

first: Alvaro

last: Curiel-Garcia

first: Elizabeth

last: Valenzuela

first: Marko

last: Jovanovic

first: Alejandro

last: Chavez


title: A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.

city: New York City

first: Alessandro

last: Vasciaveo

address: 1130 Saint Nicholas Ave., 910

department: Department of Systems Biology

institute: Columbia University

summary: Although most prostate tumors are relatively indolent, advanced disease can progress to aggressive, often lethal variants, including neuroendocrine prostate cancer (NEPC). To identify drivers of aggressive prostate cancer, we used Sleeping Beauty (SB) transposon mutagenesis in a mouse model having prostate-specific loss of Pten and Tp53 (NPp53 mice). Compared with control NPp53-SB(—) mice, experimental NPp53-SB(+) mice developed more aggressive tumors with increased metastasis. Notably, NPp53-SB(+) mice exhibited NEPC phenotypes with transcriptomic features that recapitulate human NEPC. Analysis of recurrent common insertion sites (CIS) and associated genes (CIS-genes) identified genes differentially expressed between NEPC and non-NEPC tumors. Analysis of NEPC-enriched CIS genes by cross-species integration of genomic and transcriptomic data prioritized Sirtuin 1 (Sirt1) as a candidate mechanistic determinant of NEPC. Gain- and loss-of-function studies in human prostate cancer cells and mouse NEPC organoids confirmed that SIRT1 promotes NEPC, while pharmacological inhibition suppresses it. Thus, integration of cross-species analyses with an unbiased forward genetic screen uncovered novel drivers of NEPC.


title: A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer [RNA-Seq]

summary: Advanced prostate cancer is often associated with the emergence of more aggressive disease phenotypes, including neuroendocrine prostate cancer (NEPC), which are currently incurable. To identify drivers of aggressive prostate cancer, we conducted a Sleeping Beauty (SB) transposon mutagenesis screen based on a mouse model having conditional loss of function of Pten and Tp53 prostate (NPp53). Compared with the control mice (NPp53-SB(—)), the experimental mice (NPp53-SB(+)) develop aggressive prostate cancer phenotypes that are highly heterogeneous and highly metastasis. Most notably, a high percentage of NPp53-SB(+) prostate tumors have features of NEPC, which are conserved with human prostate cancer. To identify and prioritize drivers of NEPC in these NPp53-SB(+) tumors, we used a novel integrative approach that combines (i) genomic analyses of common insert sites (CIS) for the SB transposon, (ii) VIPER analyses of control NPp53-SB(+) prostate tumors to identify master regulators (MRs) enriched in NEPC, and (iii) comparative transcriptomic analyses with data from human prostate cancer patients followed by integrative analyses using of these data using a CINDy algorithm to identify CIS-associated genes that modulate the NEPC phenotypes. Among these the nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase, sirtuin 1 (Sirt1). Loss- and gain-of-function studies in human prostate cancer cell lines showed that SIRT1 promotes NEPC, while its depletion or inhibition reduces NEPC. Overall, this integrative phenotypic and systems analyses have identified of candidate drivers of NEPC and may be generalizable to analyzing and interpreting data from analogous in vivo mutagenesis screens.

overall_design: To perform the Sleeping beauty (SB) mutagenesis screen, we used the NPp53 mice (for Nkx3.1CreERT2/+; Ptenflox/flox; Trp53flox/flox) (Fig. 1A). These mice develop prostate adenocarcinoma that progresses to CRPC following androgen deprivation (via castration) and that can further progress to advanced prostate cancer phenotypes, including NEPC, following treatment with second generation the anti-androgens (ref). We, therefore, reasoned that this GEMM would serve as an excellent model to screen for drivers of advanced prostate cancer. As a control, we used the NP mice (for Nkx3.1CreERT2/+; Ptenflox/flox), which develop well-differentiated prostate adenocarcinoma that develops CRPC following androgen deprivation but does not progress to more advanced phenotypes following treatment with second generation anti-androgens (ref). Activation of the Nkx3.1CreERT2 allele via tamoxifen induction leads to temporal and spatial recombination of Pten and/or Trp53 specifically in the prostatic epithelium

first: Francisca

middle: N

last: de Almeida

first: Andrea

last: Califano

first: Cory

last: Abate-Shen


title: RNA methyltransferase 3 drives pancreatic acinar cell carcinoma growth and is a therapeutic target

status: Public on Apr 12 2026

city: Suita

first: Shotaro

last: Tatekawa

address: 2-2(D10), Yamadaoka, Suita-city

department: Departments of Radiation Oncology,

institute: The University of Osaka Graduate School of Medicine

summary: Pancreatic acinar cell carcinoma (ACC) represents a rare and aggressive malignancy with poorly understood molecular mechanisms. N6-methyladenosine (m6A) RNA modification, particularly through the methyltransferase METTL3, has emerged as a critical regulator in various cancers. This study investigates the role of METTL3-mediated RNA methylation in ACC development and progression. We utilized transgenic mouse models over-expressing Mettl3 and SV40 large T antigen under the pancreatic Elastase I promoter. Comprehensive analyses included m6A-methylated RNA immunoprecipitation sequencing (MeRIP-seq), single-cell RNA sequencing (scRNA-seq), and functional studies with the METTL3 inhibitor STM2457. SAM-binding domain deletion mutants were generated to assess functional requirements. Mettl3 overexpression significantly accelerated ACC development and enhanced tumor aggressiveness. The SAM-binding domain proved essential for tumor formation, as deletion mutants failed to promote carcinogenesis. MeRIP-seq revealed preferential methylation of cell cycle and DNA replication genes in Mettl3-overexpressing tumors. scRNA-seq analysis demonstrated enhanced malignancy signatures, including epithelial-to-mesenchymal transition and TGF-β signaling. METTL3 promoted PRSS1-mediated signaling from ACC cells to inflammatory cancer-associated fibroblasts, creating a feed-forward loop involving IGF1 that amplifies tumor growth. Conditional Mettl3 deletion induced rapid tumor apoptosis. Pharmacological inhibition with STM2457 similarly triggered caspase-3/7-dependent apoptosis in pancreatic tumors. METTL3-mediated RNA methylation drives ACC pathogenesis through tumor-intrinsic cell cycle regulation and tumor-extrinsic stromal interactions. These findings establish METTL3 as a promising therapeutic target and provide mechanistic insights supporting clinical development of METTL3 inhibitors for pancreatic cancer treatment.

overall_design: Single-cell RNA-seq data for the following mouse tumor samples: WTg (TAg/Mettl3) and EL (TAg)

first: Tomoaki

last: Hara

first: Sikun

last: Meng

first: Tetsuya

last: Sato

first: Hideshi

last: Ihii


overall_design: RIP-seq data using m6A antibody for the following mouse tumor and liver samples: Kras/Mettl3, TAg/Mettl3, TAg/Mettl3-depleted, and TAg


title: A Pilot Phase II Study of Neoadjuvant Fulvestrant plus Abemaciclib in Women with Advanced Low-Grade Serous Carcinoma

city: Houston

first: Sanghoon

last: Lee

address: 1881 East Road

institute: The University of Texas MD Anderson Cancer Center

summary: Neoadjuvant chemotherapy shows limited activity in low-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (LGSOC). Given LGSOC’s similarities to hormone receptor-positive (HR+) breast cancer, including clinical benefit from endocrine therapies, we conducted a phase II pilot study to assess the clinical benefit of neoadjuvant treatment with fulvestrant and abemaciclib for women with advanced LGSOC. Women with untreated, unresectable stage III or IV LGSOC were eligible. Patients received fulvestrant (500 mg IM on day 1 and 15 of the first 28-day cycle, then day 1 of subsequent cycles) and abemaciclib 150 mg orally BID. Pre/perimenopausal patients received goserelin 10.8 mg subcutaneously every 12 weeks for ovarian suppression. Imaging re-assessment was performed every 8 weeks using RECIST 1.1 until deemed resectable. Following interval cytoreductive surgery (ICS), patients received 4 cycles of adjuvant fulvestrant and abemaciclib followed by maintenance letrozole. Patients with progressive disease were removed from the study and received standard chemotherapy. The primary endpoint is best overall response clinical benefit rate (BOR CBR). Fifteen patients were enrolled and evaluable for efficacy. BOR CBR in the neoadjuvant setting was 100%, with 9/15 patients (60%) achieving partial response (PR), and 6/15 patients (40%) showing stable disease (SD). One patient with radiologic PR had pathologic complete response at ICS. Nine of fifteen patients (60%) underwent ICS – 5 (55.5%) with complete gross resection, 2 (22.2%) with <1cm residual disease, and 2 (22.2%) with suboptimal cytoreduction. Median time on study prior to surgery was 8.38 months. Neoadjuvant treatment with fulvestrant and abemaciclib was tolerable and demonstrated unprecedented response and CBR rates in this pilot study. These results compare favorably with published outcomes of neoadjuvant chemotherapy in LGSOC.

overall_design: Three pairs of pre- and post-treatment samples were subject to RNA sequencing.

first: Yibo

last: Dai

first: Linghua

last: Wang

first: Lauren P.

last: Cobb

first: Amir A.

last: Jazaeri


title: DYRK1A enhances antitumor immunity in type 1 conventional dendritic cells via mTORC1 activation [tumor-infiltrating type 1 conventional dendritic cells]

status: Public on Apr 10 2026

city: Xiamen

first: Hongjiao

address: xiangannanlu

institute: xiamen university

summary: Type 1 conventional dendritic cells (cDC1s) play an integral role in mediating immune responses and maintaining homeostasis, yet the molecular mechanisms underlying their functions remain poorly understood. In this study, we identified dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) as a key kinase that responded to TLR and growth factor stimulation and acted as an essential regulator of cDC1 function. Genetic ablation of Dyrk1a specifically in cDC1s impaired antitumor immunity and accelerated tumor progression in murine models. Mechanistically, DYRK1A mediated the phosphorylation of the mTORC1 inhibitor TSC2 at serine 540, triggering the degradation of TSC2 and promoting the mTORC1 signaling in cDC1s. Notably, Tsc2 deletion in Dyrk1a-deficient cDC1s remarkably restored their antitumor immune functions. Furthermore, DYRK1A-mediated mTORC1 signaling in cDC1s positively correlated with effector T-cell responses across multiple human cancers. Our findings highlight a critical role for the DYRK1A-TSC2-mTORC1 signaling pathway in regulating cDC1 functions in antitumor immunity, offering potential strategies to improve cancer immunotherapy.

overall_design: For RNA-seq profiling, tumor-infiltrating cDC1s (CD3-CD19-NK1.1-Ly6C-Ly6G-F4/80-CD11c+XCR1+) were sorted from tumor tissues of B16-F10 tumor-bearing Dyrk1a+/+-Cd11c-cre and Dyrk1afl/fl-Cd11c-cre mice (day 13 after tumor cell inoculation).

first: Songlin

last: He

first: Pan

last: Zhu

first: Zuliang

last: Jie


title: Molecular signatures of maladaptive plasticity in the amygdala in a rat model of chronic neuropathic pain

city: Lubbock

first: Julian

middle: David

last: Cardenas

address: 3601 4th Street

department: Pharmacology and Neurosciences

institute: Texas Tech University Health Science Center

summary: Chronic pain, a complex multidimensional disorder, remains a major health care issue and a therapeutic challenge. Neuropathic pain is a chronic pain condition that results from damage or dysfunction in the nervous system. While mechanisms of neuropathic pain at the peripheral and spinal cord level have been extensively studied, pain mechanisms in the brain remain underexplored. The amygdala, a limbic brain region, has emerged as a critical brain area for the emotional-affective dimension of pain and pain modulation. Amygdala neuroplasticity has been associated with pain states, but exact molecular and cellular mechanisms underlying these states and the transition from acute to chronic pain are not well understood.We used an integrative approach that focuses on functional significance and cell type specificity of differentially expressed genes (DEGs) to nominate mechanistic targets for central regulation of chronic pain. Our integrative transcriptomic and bioinformatic analyses identified individual genes (e.g., Cxcl10, Cxcl12, Mbp, Plp1, Mag, Mog, Slc17a6, Gad1, Sst), molecular pathways (e.g., cytokine-mediated signaling pathway), biological processes (e.g., myelination, synaptic transmission), and specific cell types (e.g., oligodendrocytes, glutamatergic and GABA-ergic neurons) affected by chronic pain. Our results also provide evidence for the emerging concept of hemispheric lateralization of pain processing in the amygdala. Overall, our study proposes oligodendrocyte dysfunction in the amygdala, neuroimmune signaling in CeA, and glutamatergic neurotransmission in BLA as mechanistic determinants of and potential therapeutic targets for the management of chronic neuropathic pain.

overall_design: The well-established SNL rat model of neuropathic pain was utilized to induce a stable and long-lasting peripheral neuropathy. Rats were anesthetized with isoflurane (2-3%; precision vaporizer, Harvard Apparatus, Holliston, MA) and underwent surgery to expose and tightly ligate the left L5 spinal nerve using 6-0 sterile silk. A sham-operated control group underwent a similar surgical procedure where the L5 spinal nerve was exposed but not ligated. Topical antibiotic (Bacitracin) was applied daily for 5 days after all surgical procedures to prevent infection.

first: P

last: Presto

first: J

first: G

last: Ji

first: C

last: Bustamante

first: B

last: Kisby

first: O

last: Ponomareva

first: V

last: Neugebauer

first: I

last: Ponomarev


title: An Antagonistically Pleiotropic Gene Regulates Vertebrate Growth, Maturity and Aging

city: Jerusalem

first: Itamar

last: Harel

address: Givat Ram

department: Genetics

country: Israel

institute: The Hebrew University of Jerusalem

summary: The antagonistic pleiotropy theory of aging predicts genetic trade-offs between early-life and late-life fitness. However, empirical evidence for these trade-offs in vertebrates remains scarce, particularly in the context of ecologically relevant life histories. Here, we identify vestigial-like 3 (vgll3), a transcription cofactor previously linked with age at maturity in humans and Atlantic salmon through GWAS studies, as an antagonistically pleiotropic gene in turquoise killifish (Nothobranchius furzeri). By disrupting two conserved vgll3 isoforms, we show that reduction of vgll3, in an isoform- or dose-dependent manner, accelerated male growth and reproductive development. This indicates that vgll3 regulates male sexual maturity. However, early-life benefits come at a late-life cost, as older mutant males with a disrupted long isoform develop melanoma-like tumors, validated via transplantation into immunodeficient rag2 models, and exhibit increased age-related mortality rate. These findings highlight vgll3 as a key regulator of vertebrate life-history trade-offs, balancing early-life fitness with late-life disease risks.

overall_design: Primary cells-derived from the killifish tails. Each sample varied by genotype (wild-type, homozygous mutation in Exon1, or Exon3). Two technical replicates were used for each sample.

first: Eitan

last: Moses

first: Marva

last: Bergman

first: Tehila

last: Atlan

first: Elizabeth

last: Duxbury

first: Roman

last: Franěk

first: Omer

last: Ben Dor

first: Henrik von

last: Chrzanowski

first: Enas

last: Abu-Zhayia

first: Shay

last: Kinreich

first: Nabieh

last: Ayoub

first: Ido

last: Ben-Ami

first: Alexei

last: Maklakov


title: A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer

first: Alessandro

last: Vasciaveo

overall_design: To perform the Sleeping beauty (SB) mutagenesis screen, we used the NPp53 mice (for Nkx3.1CreERT2/+; Ptenflox/flox; Trp53flox/flox). These mice develop prostate adenocarcinoma that progresses to CRPC following androgen deprivation (via castration) and that can further progress to advanced prostate cancer phenotypes, including NEPC, following treatment with second generation the anti-androgens. We, therefore, reasoned that this GEMM would serve as an excellent model to screen for drivers of advanced prostate cancer. As a control, we used the NP mice (for Nkx3.1CreERT2/+; Ptenflox/flox), which develop well-differentiated prostate adenocarcinoma that develops CRPC following androgen deprivation but does not progress to more advanced phenotypes following treatment with second generation anti-androgens (ref). Activation of the Nkx3.1CreERT2 allele via tamoxifen induction leads to temporal and spatial recombination of Pten and/or Trp53 specifically in the prostatic epithelium

first: Francisca

last: de Almeida

first: Andrea

last: Califano

first: Cory

last: Abate-Shen


title: SPEN loss drives extra-follicular diffuse large B cell lymphoma with female-specific lethality and TLR pathway therapeutic vulnerabilities

first: Matt

last: Teater

address: 445 E 69th St

institute: Weill Cornell Medical College

summary: In this study, we explore the interplay between SPEN and NOTCH2 truncating mutations, identifying an alternative, extra-follicular, trajectory of diffuse large B cell lymphomas (DLBCL) transformation. Our findings challenge the traditional germinal centre-centric model of lymphomagenesis, showing that marginal zone B cells (MZB) can give rise to aggressive lymphomas with autoimmune/aged B cells (AiBC)-like features, under the influence of these compound mutations. At a mechanistic level, we found that SPEN loss re-routes NOTCH2-driven transcriptional programs, promoting a ZEB2-driven cell fate that blocks plasmacytic differentiation and skews B cell identity toward a MZB/AiBC mixed phenotype. We further show that SPENTRUNC/NOTCH2TRUNC-mutant lymphomas are associated with reduced overall survival of female DLBCL patients, due to X-chromosomal transcriptional perturbations. By characterizing their unique molecular dependencies, we identify actionable features in this aggressive DLBCL subset, paving the way for new precision medicine strategies that address the disease’s heterogeneity.

overall_design:
RNAseq in murine germinal center B cells, tFL cell line model, PDX samples

scRNA and scATAC-Seq of sorted splenic MZB/FOB/AiBCs of female, unimmunized mice.

SMRT-Seq of CD19+ enriched lymphoma samples from female WT MZB, N2 and SN2 lymphomas

first: Benedikt

last: Pelzer

first: Cem

last: Meydan

first: Ari

last: Melnick


title: Epitranscriptomic analysis reveals clinical and molecular signatures in glioblastoma

city: Miami

first: Glaucia Maria

middle: de

last: Mendonça Fernandes

state: FL

address: 4060 SW 97th PL

department: HWCOM Cellular and Molecular Medicine

institute: Florida International University

summary: Retrospective GB patient data of patients that were eventually deemed to have progressive disease or pseudoprogressive disease was captured from the electronic health record , and RNA from the first resection specimen was utilized to evaluate Arraystar Human m6A Single Nucleotide resolution microarray analysis  biomarkers from FFPE samples

overall_design: 92 patients were categorized into psPD and PD groups: psPD was identified by new or progressive enhancement within 6 months of ChemoRT, confirmed treatment reaction, and no prior progression. PD classification relied on clinic-pathologically confirmed cancer recurrence with no previous progression history

first: Fernandes

last: Glaucia Maria de Mendonça Fernandes

first: Wang

last: Wesley

first: Jones

last: Daniel

first: Peng

last: Jing

first: Giglio

last: Pierre

first: Venere

last: Monica

first: Otero

last: Jose Javier


title: Mechanistic target of rapamycin/blood test barrier mechanism mediates acceleration of sperm epigenetic aging by environmental factors.

status: Public on Apr 30 2026

city: Amherst

first: Alexander

last: Suvorov

address: Environmental Health Sciences Department

institute: University of Massachusetts Amherst

type: Methylation profiling by genome tiling array

summary: Our previous research suggested that mechanistic target of rapamycin (mTOR)/blood-testis barrier (BTB) mechanism is involved in the regulation of the rates of epigenetic aging of sperm, where increased activity of mTORC1 opens BTB and accelerates epigenetic aging and increased activity of mTORC2 produces opposite results – increases BTB integrity and rejuvenates sperm epigenome. In the current study using newly developed epigenetic clock model we tested if this mechanism is involved in epigenetic reprograming of sperm in mice by heat stress (HS) and Cd exposure. We demonstrate that mTOR-dependent BTB disruption by HS and mTOR-independent BTB disruption by Cd accelerate epigenetic aging of sperm and produce similar effects on sperm DNA methylation. Thus, we identified the novel molecular mechanism that mediates effects of environmental stressors on sperm epigenetic aging and may be common to a broad range of environmental, lifestyle, dietary, health and other factors.

overall_design: C57BL6 male mice of different age were used for sperm epigenetic clock model development or for exposure experiments. For sperm epigenetic clock (Non-treatment group), animals of 15 different ages as follows (postnatal day – number of mice): 69 - 4, 80 - 4, 107 - 4, 118 - 3, 165 - 2, 186 - 1, 190 - 4, 225 - 3, 252 - 1, 265 - 4, 276 - 4, 291-3, 300 - 1, 330 - 4, and 334 - 4. For treatment groups, twenty 100-days old mice were assigned to one of the following groups (n = 5 per group): 34.5°C HS or cadmium (Cd) group.

first: Olatunbosun

last: Arowolo

first: Oladele

last: Oluwayiose

first: Jiahui

last: Zhu

first: Oleg

last: Sergeyev

first: Emily

last: Houle

first: J

last: Pilsner


title: Exploring life-long tissue homeostasis through lineage tracing and cell transplantation

first: Itamar

last: Harel

summary: Using lineage tracing and fate mapping strategies to study vertebrate aging has lagged behind developmental studies, primarily due to of the relatively long lifespans of classical models. Here, we introduce the Killibow, an inducible transgenic model for in-vivo multicolor lineage tracing in the naturally short-lived turquoise killifish (N. furzeri). We demonstrate that Cre-mediated recombination in transgenic fish can generate robust and stochastic labeling that remains stable during aging and regeneration. In addition, to achieve inducible control of recombination, we either utilize in-vivo Cre electroporation or use the tamoxifen system in Killibow-derived cells. To further enable transplantation assays, we establish the first immunocompromised killifish model by mutating rag2. RNA sequencing reveals that rag2 mutants exhibit severely compromised expression of V(D)J recombination products, including immunoglobulins. Accordingly, we demonstrate that clearance of transplanted Killibow-derived cells is delayed in rag2 recipients, and present a proof-of-principle for a KRAS G12D cancer model that is compatible with lineage tracing. Our platform provides the opportunity to examine tissue homeostasis, stem cell function, cancer dynamics, and tissue regeneration at unprecedented temporal resolution during vertebrate aging and disease.

overall_design: We compared the transcriptome of the killifish head kidney, the equivalent of the mammalian bone marrow, from three wild-type and three rag2 mutants.

first: Itai

last: Rozenberg

first: Tehila

last: Atlan

first: Roman

last: Franek

first: Eitan

last: Moses

first: Adi

last: Oron-Gottesman

first: Henrik

last: Chrzanowski


title: Transcriptomic Profiling of RAW264.7 Cells During RANKL-Induced Osteoclast Differentiation

status: Public on Apr 09 2026

city: Hefei

first: sijie

last: bian

address: Huaihai Avenue

department: Department of Orthopaedics

institute: The First Affiliated Hospital of Anhui Medical Universit

summary: Osteoclast differentiation is primarily driven by RANKL stimulation, yet the transcriptional remodeling associated with this process remains incompletely characterized. This dataset profiles global gene expression changes in RAW264.7 macrophages under two conditions: untreated control and RANKL-induced osteoclast differentiation. The transcriptomic comparison reveals key pathways associated with osteoclast formation, including osteoclast-related gene activation, metabolic remodeling, and oxidative stress–related signaling. These data serve as the baseline reference for subsequent uridine-intervention analyses.

overall_design: This study analyzed six RNA-seq samples from RAW264.7 murine macrophages. Two experimental conditions were included: untreated control and RANKL-stimulated osteoclast differentiation. Each condition contained three biological replicates. Total RNA was collected after 3 days of culture and subjected to high-throughput sequencing to compare transcriptomic changes associated with RANKL-induced osteoclastogenesis.

first: Sijie

last: Bian


title: Uridine Modulates Gene Expression Programs During RANKL-Induced Osteoclastogenesis in RAW264.7 Cells

summary: Uridine has been implicated in the regulation of metabolic and redox processes, yet its transcriptional effects during osteoclast differentiation remain unclear. This dataset profiles global gene expression in RAW264.7 cells under three conditions: untreated control, RANKL-induced osteoclastogenesis, and RANKL combined with uridine treatment. The results reveal uridine-responsive transcriptional changes involving osteoclast differentiation, oxidative stress regulation, and PI3K/Akt–FoxO–related pathways, providing mechanistic insight into uridine-mediated modulation of osteoclastogenesis.

overall_design: This study analyzed nine RNA-seq samples from RAW264.7 murine macrophages. Three experimental conditions were included: untreated control, RANKL-induced osteoclast differentiation, and RANKL combined with uridine treatment. Each condition contained three biological replicates. Total RNA was collected after 3 days of culture and sequenced to evaluate transcriptional changes associated with uridine-mediated regulation of osteoclastogenesis.


title: A circuit of mechanically regulated transcription factors balances regenerative and fibrotic memory of mesenchymal stromal cells

city: Charlottesville

first: Andrew

last: Miller

state: Virginia

address: 415 Lane Rd.

department: Biomedical Engineering

institute: University of Virginia

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

overall_design: Refer to individual Series


title: Tet governs transcriptional programs required for intestinal stem cell development and homeostasis

first: Hongjie

last: Li

address: One Baylor Plaza

institute: Baylor College of Medicine

summary: For two decades, Drosophila intestinal stem cells (ISCs) have served as a premier model for studying somatic stem cell biology. Yet, the intrinsic mechanisms driving divergent developmental trajectories of seemingly homogeneous progenitors, directing some to establish adult ISCs and others to differentiate, remain unclear. Here, we identify Tet as an essential transcriptional regulator of ISC establishment. Developmental Tet depletion causes region-specific ISC loss and compromises adult lifespan, while adult-specific loss drives progressive stem cell exhaustion. Overexpression of Tet leads to ISC expansion in both developing and adult guts. Utilizing a comprehensive single-nucleus transcriptomic atlas spanning gut development, we demonstrate that Tet stabilizes progenitor identity by maintaining epithelial integrity, signaling competence, and fate maintenance. By defining this developmental trajectory, we reveal Tet as a critical factor that drives proper ISC maturation and maintains long-term adult epithelial homeostasis.

overall_design:
Single-nucleus RNA-sequencing
Midgut samples were collected from females across each stage: wandering third instar larva (L3), white prepupa (P0), 18hr pupa (P18), 48hr pupa (P48), and day 2 adults (D2).
Genotypes: esg-GAL4/Luciferase RNAi, esg-GAL4/dTet RNAi

first: Niccole

last: Auld

first: Ye-Jin

last: Park

first: Yanyan

last: Qi


title: A circuit of mechanically regulated transcription factors balances regenerative and fibrotic memory of mesenchymal stromal cells [RNA-seq]

summary: Therapeutic mesenchymal stromal cells (MSCs) are used to support the healing of severe injuries such as skin burn wounds. However, the pivotal expansion from donor biopsies on conventionally stiff culture surfaces activates MSCs into scar-promoting myofibroblasts. We previously coined the term mechanical memory to describe that priming of MSCs on scar-stiff culture substrates imprints myofibroblast features that persist even after a switch to skin-soft substrates. We now unravel mechanisms and factors that, conversely, suppress myofibroblast activation upon priming in skin-soft expansion culture. Such ‘soft memory’ factors are poised to preserve MSC regenerative features while suppressing fibrogenesis. Mechanically primed MSCs were compared by RNA- and assay for transposase-accessible chromatin (ATAC)-sequencing. The promoters of genes that were highly accessible and upregulated upon soft priming and memorized after switch to stiff substrates were significantly enriched for motifs predicted to bind the transcription factor HOXA11. Knockdown of HOXA11 resulted in enhanced expression of fibrogenic and osteogenic genes in soft-primed MSCs and reduced expression of anti-fibrotic factors, including the transcription factor SALLl1. SALL1 is a potent suppressor of pro-fibrotic genes such as Postn, Col8a1, Grem2, Thps1 and Thps2, and the transcription factor Gata6. GATA6, in turn, emerges as a keeper of stiff-induced myofibroblast memory by maintaining the accessibility of pro-fibrotic genes even after switch to soft substrates. By manipulating the SALL1-GATA6 transcriptional circuit in culture, we produced therapeutic MSCs that suppress fibrosis in an animal model of hypertrophic skin scarring. We propose that similar control over myofibroblast memory will enhance the success of therapeutic MSC applications in organ repair.

overall_design: RNA-sequencing of rat bone marrow-dervied mesenchymal stromal cells (MSCs) cultured on 2kPa or 100kPa gelatin-coated silicone elastomer substrates for 1, 3, or 5 passages. Passages were performed once per week. To evaluate the role of mechanical memory in the maintenance of the chromatin accessibility landscape, MSCs were cultured on 2kPa or 100kPa substrates for 3 passages and transferred to 100kPa (2T100_4) or 2kPa substrates (100T2_4) for 2 additional passages, respectively.

first: Fereshteh

last: Younesi

middle: E

first: Natalie

last: Andonian

first: Li

last: Diao

first: Thomas

middle: H

last: Barker

first: Boris

last: Hinz


title: Early-life nutritional imbalance impairs colonic epithelial regeneration through gut microbiota dysbiosis and metabolic suppression

status: Public on Apr 26 2026

city: Yangzhou

first: Yimin

last: Zhuang

state: Jiangsu

address: No. 88, Daxue South Road

institute: Yangzhou University

summary: Childhood malnutrition represents a major global health burden that extends beyond caloric deficiency to include dietary imbalance. The early-life gut microbiome functions as a dynamic ecosystem whose structure and metabolic output are intimately linked to host development, yet how nutritional imbalance disrupts this ecosystem and its integration with the host remains poorly understood.

overall_design: A total of 30 three-week-old female specific pathogen-free (SPF) C57BL/6J mice (Sibeifu Biotechnology Co., Ltd., China) were used in the experiment and underwent a 7-day acclimation period before treatment.


title: LPS-induced lncRNA expression profiling in human PBMC-derived macrophages

city: Boston

first: DAIKI

last: HOSOKAWA

state: MA

address: 3 Blackfan Street, 17th Floor

department: Center for Interdisciplinary Cardiovascular Sciences

institute: Brigham and Women's Hospital

type:
Expression profiling by array
Non-coding RNA profiling by array

summary: Introduction: Macrophages play a key role in inflammatory diseases. We aimed to identify long noncoding RNAs that regulate pro-inflammatory activation of human macrophages.  Methods: We performed human lncRNA microarray analysis in LPS-stimulated primary human macrophages. We then carried out loss-of-function and gain-of-function experiments, luciferase reporter assays, RNA pulldown, RNA immunoprecipitation, and mouse endotoxemia studies, including humanized mouse models.  Results: We identified 11 lncRNAs that were significantly increased by LPS. Among them, lnc-FAM164A1 was selected for further study. Silencing of lnc-FAM164A1 by antisense oligonucleotides or siRNA reduced the LPS-induced expression of pro-inflammatory cytokines, including CCL2, IL-6, and TNF-a. In contrast, enforced expression of lnc FAM164A1 enhanced inflammatory responses in human and mouse macrophages. lnc FAM164A1 also promoted NF-kB-related signaling. RNA pulldown and RNA immunoprecipitation identified ACLY as an lnc-FAM164A1-  associated protein. ACLY silencing reduced the inflammatory effects induced by lnc-FAM164A1.  Discussion: These findings support that human lnc-FAM164A1 promotes pro-inflammatory activation of macrophages through its interaction with ACLY and NF-kB-related signaling.

overall_design: 8 RNA samples from human PBMC-derived macrophages were analyzed. Four samples were untreated control samples (CtrlA, CtrlB, CtrlC, and CtrlD), and four samples were treated with 10 ng/mL LPS for 3 hours (TreatE, TreatF, TreatG, and TreatH).

first: Masanori

last: Aikawa

first: Daiki

last: Hosokawa


title: Bulk RNA-seq Toxic Lipid-induced Epigenetic Activation of ICAM1 in Liver Sinusoidal Endothelium Regulates Myeloid-Driven Fibro-inflammatory Response in MASH

status: Public on Apr 27 2026

city: Rochester

first: Alexandra

last: Krivonos

state: MN

address: 200 1st St SW

department: Quantitative Health Sciences

institute: Mayo Clinic

summary: Background: Liver sinusoidal endothelial cells (LSECs) acquire a proinflammatory phenotype in metabolic dysfunction-associated steatohepatitis (MASH), characterized by elevated adhesion molecules and inflammatory mediators—a process termed lipotoxic endotheliopathy. However, the molecular drivers of this transformation remain incompletely defined. Methods: We employed complementary models of lipotoxicity and MASH, including palmitate-treated primary human LSECs (in vitro), cultured precision-cut liver slices from normal human and mice liver with MASH-inducing media as well as MASH mice (ex vivo), and diet-induced MASH models (in vivo). Results: GeoMx digital spatial profiling of human MASH livers revealed enriched proinflammatory and fibrogenic signaling between LSECs and myeloid cells. Among the top upregulated genes and ligand-receptor pairs was ICAM1, whose expression correlated with disease severity and was increased in human MASH by immunostaining. ATAC-seq on primary mouse LSECs showed enhanced chromatin accessibility at the Icam1 promoter in MASH. Chromatin immunoprecipitation confirmed enrichment of the active epigenetic mark H3K27ac and BRD4 binding at the ICAM1 promoter in human LSECs under lipotoxic stress. Mechanistically, we identified the GSK3β/c-Jun/BRD4 axis as a key regulator of ICAM1 induction in LSECs. In vivo, ICAM1-neutralizing antibody or endothelial-specific epigenetic suppression reduced hepatic inflammation, injury, and fibrosis in MASH mice. Conclusion: ICAM1 is epigenetically upregulated in LSECs during lipotoxic stress and promotes myeloid cell recruitment in MASH. Targeting the epigenetic regulation of ICAM1 may offer a novel therapeutic strategy for treating human MASH.

overall_design: Primary human LSECs (HHSEC) treated with vehicle, 500µM PA, 800µM PA or 800 µM PA+LY, overnight. Total RNA was prepared for bulk RNA-sequencing.

first: Qianqian

last: Guo

first: Nantawat

last: Satthawiwat

first: Akitoshi

last: Sano

first: Chady

last: Meroueh

first: Asma

last: Hamdi

first: Xin

last: Dai

first: Khaled

last: Warasnhe

first: Alexander

last: Washington

first: Patrick

last: Starlinger

first: Alex

first: Sheng

last: Cao

first: Enis

last: Kostallari

first: Johan

middle: W

last: Jonker

first: Bart

last: van de Sluis

first: Feda

last: Hamdan

first: Samar

last: Ibahim


title: Oncolytic vaccinia virus JX-594 demonstrates subtype-specific efficacy and predictive biomarkers in gastric cancer cell lines

city: 강남구

first: Inho

last: Park

state: 서울특별시

address: Dept. of Pathology, Gangnam Severance Hospital, 20, Eonjuro 63gil

department: Yonsei University College of Medicine

country: South Korea

institute: Yonsei University College of Medicine

summary: This project investigates the therapeutic potential of the oncolytic vaccinia virus JX-594 in gastric cancer. We analyzed 49 molecularly characterized GC cell lines and xenograft models, and performed transcriptomic profiling to identify subtype-specific responsiveness and explore predictive biomarkers that may guide clinical application.

overall_design: RNA-seq was performed for 49 molecularly characterized gastric cancer cell lines. Total RNA was extracted using the RNeasy Mini Kit (Qiagen), quality-assessed with NanoDrop and Bioanalyzer, and sequenced on the Illumina HiSeq 2500 platform using 2×100 bp paired-end reads.

first: Jee Hung

last: Kim

first: YeLin

first: Youkeun

last: Shin

first: Woo Sun

last: Kwon

first: Tae Soo

first: Namhee

last: Lee

first: Keunhee

last: Oh

first: Chan

first: Hei-Cheul

last: Jeung

first: Sun Young

last: Rha


title: A circuit of mechanically regulated transcription factors balances regenerative and fibrotic memory of mesenchymal stromal cells [ATAC-Seq]

first: Andrew

last: Miller

overall_design: ATAC-sequencing of rat bone marrow-dervied mesenchymal stromal cells (MSCs) cultured on 2kPa or 100kPa gelatin-coated silicone elastomer substrates for 1, 3, or 5 passages. Passages were performed once per week. To evaluate the role of mechanical memory in the maintenance of the chromatin accessibility landscape, MSCs were cultured on 2kPa or 100kPa substrates for 3 passages and transferred to 100kPa (2T100_4) or 2kPa substrates (100T2_4) for 2 additional passages, respectively.

first: Fereshteh

last: Younesi

first: Natalie

last: Andonian

first: Li

last: Diao

first: Thomas

last: Barker

first: Boris

last: Hinz


title: EZH2 Blockade Reverses Doxorubicin Resistance by Disrupting Metabolic and DNA Repair Networks in Breast Cancer

status: Public on Apr 08 2026

city: Tianjin

first: Chen

last: Wenlong

state: 天津市

address: No. 23 Pingjiang Road, Hexi District

institute: 天津医科大学第二医院

summary: Background: Doxorubicin (DOX) resistance remains a major obstacle to effective chemotherapy in breast cancer. However, the pharmacologically actionable regulators sustaining this resistant phenotype and its therapeutic vulnerabilities remain incompletely defined. Methods: DOX-resistant breast cancer cell models were established and treated with the EZH2 inhibitors tazemetostat or GSK126, alone or in combination with DOX. Cell viability, oxidative stress, DNA damage, and mitochondrial function were assessed in vitro. Transcriptomic profiling was performed to identify pathway alterations. A pH-responsive liposomal system for delivery of DOX and tazemetostat was developed and evaluated in vivo. Results: EZH2 was highly expressed in breast cancer and correlated with poor clinical outcomes. DOX treatment induced adaptive upregulation of EZH2 in both sensitive and resistant cells. Pharmacological inhibition of EZH2 markedly restored DOX sensitivity and exhibited strong synergistic cytotoxicity in resistant models. EZH2 blockade enhanced DOX-induced oxidative stress and DNA damage, with concomitant suppression of multiple DNA repair pathways and increased γH2AX accumulation. Transcriptomic and functional analyses revealed disrupted mitochondrial function and energy metabolism, characterized by loss of mitochondrial membrane potential and ATP depletion. In vivo, combined EZH2 inhibition and DOX significantly suppressed tumor growth, while pH-responsive liposomal delivery further enhanced antitumor efficacy and reduced systemic toxicity. Conclusion: EZH2 is a critical determinant of DOX resistance in breast cancer by sustaining DNA damage tolerance and metabolic homeostasis. Pharmacological targeting of EZH2 in combination with DOX represents a rational strategy to overcome chemoresistance in breast cancer.

overall_design: RNA-seq profiling of DOX-resistant breast cancer cells (231-ADR) treated with EZH2 inhibitors (TAZ or GSK126), doxorubicin (DOX), or their combination to investigate changes in oxidative stress, DNA damage repair, and metabolic pathways.

first: Xiaomin

last: Wang

first: Yunxiao

last: Mai

first: Yuhang

last: Ding

first: Wenlong

last: Chen


title: Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration

city: Geneva

first: Hanrong

last: Hu

address: B1 0 266.045 (Campus Biotech bâtiment B1)

department: Brain Mind Institute

institute: EPFL

summary: Why mammals cannot regenerate limbs, unlike amphibians, presents a longstanding puzzle in biology. We show that exposing ex vivo amputated embryonic mouse limbs to subatmospheric oxygen environment, or stabilizing oxygen-sensitive HIF1A enables not only rapid wound healing, but alters cellular mechanics, and reshapes the histone landscape to prime regenerative fates. Conversely, regenerative Xenopus tadpole limbs display low oxygen-sensing capacity, robust wound healing, a regenerative histone landscape, and glycolytic programs even under high oxygen. This reduced oxygen-sensing capacity, in stark contrast to mammals, associates with decreased HIF1A-regulating gene expressions. Our findings thus uncover species-specific oxygen sensing as a unifying mechanism for limb regeneration initiation across vertebrates, reveal how aquatic subatmospheric habitats may enhance regenerative capabilities, and identify targetable barriers to unlock latent limb regenerative programs in adult mammals.

sample_organism:
Xenopus laevis
Mus musculus

platform_organism:
Xenopus laevis
Mus musculus

overall_design: CUT&Tag of mouse and xenopus limb explants cultured at hypoxic or atmospheric oxygen levels

first: Kelly

first: Aztekin

last: Can