title: Effects of Rg3@PACVs with NIR in a Rat Model of Pulmonary Ischemia–Reperfusion Injury

city: guangzhou

first: Haoxiang

last: Yuan

address: 28 Qiaozhong Middle Road, Liwan District

department: Department of Thoracic Surgery and Oncology

institute: The First Affiliated Hospital of Guangzhou Medical University

summary: Pulmonary ischemia–reperfusion injury (IRI) is characterized by excessive inflammation, oxidative stress, and mitochondrial dysfunction, leading to severe lung damage. To elucidate the molecular mechanisms underlying the protective effects of a macrophage membrane-coated mesoporous polydopamine nanoparticle system loaded with Ginsenoside Rg3 (Rg3@PACVs) combined with near-infrared (NIR) irradiation, we performed transcriptome sequencing of rat lung tissues. Differential gene expression profiles were compared between IRI and IRI + Rg3@PACVs + NIR groups. A total of 209 upregulated and 332 downregulated genes were identified in the treatment group relative to IRI controls. Functional enrichment analyses revealed that Rg3@PACVs + NIR pretreatment enhanced pathways related to endoplasmic reticulum stress response, PI3K-AKT signaling, oxygen transport, protein folding, hypoxia response, TCA cycle activity, ATP-dependent processes, and cell cycle progression. In contrast, inflammation-associated pathways including TLR/NF-κB signaling, cytokine binding, cell adhesion molecules, neutrophil extracellular trap formation, IL-1β production, and leukocyte trans-endothelial migration were significantly suppressed. GSEA further demonstrated reduced oxidative stress (cytochrome P450 activity) and enhanced FOXO signaling. These findings indicate that Rg3@PACVs + NIR mitigates pulmonary IRI by coordinately suppressing inflammatory responses, alleviating oxidative stress, and restoring mitochondrial homeostasis, thereby promoting lung tissue repair.

overall_design: The male SD rats were subjected to pulmonary ischemia–reperfusion injury and randomly assigned to two groups: IRI (n = 3) and IRI + Rg3@PACVs + NIR (n = 3). Total RNA was extracted from the left lung tissues for high-throughput sequencing.

first: Bo

first: Pu

last: Shen

first: Jiancheng

last: Deng

first: Ying

first: Meiyu

last: Huang

first: Wentao

last: Wu

first: Xin

last: Xu

first: Xuanlin

last: Zhang

first: Xue

first: Xudong

first: Zhijin

last: Fan

first: Jianxing

last: He


title: Single-cell and Spatial Transcriptomic Profiling of the Bone Metastatic Microenvironment

status: Public on Mar 11 2026

city: Houston

first: Li

last: Yang

address: 6565 Fannin Street

department: Department of System Medicine and Bioengineering (SMAB)

country: USA

institute: METHODIST HOSPITAL RESEARCH INSTITUTE

type: Expression profiling by high throughput sequencing

summary: The goal of this study is to comprehensively characterize the cellular composition, transcriptional programs, and spatial organization of the bone metastatic microenvironment and to assess how therapeutic perturbation influences tumor–microenvironment interactions. A mouse bone metastasis model was established via internal iliac artery injection of Lewis lung carcinoma cells, and metastatic lesions were monitored by in vivo imaging. Single-cell RNA sequencing and 10x Genomics Visium–based spatial transcriptomics were generated from metastatic bone tissues to provide complementary cellular and spatial resolution.

overall_design: Mouse bone metastasis samples were generated using an internal iliac artery (IIA) injection model. Mice were maintained under standard laboratory housing conditions with ad libitum access to food and water. Bone metastases were induced by injection of LLC1 tumor cells, and animals were monitored post-procedure until full recovery. Bone tissues were harvested at defined experimental endpoints for downstream single-cell RNA sequencing and spatial transcriptomics analysis. For the details, please refer to Wang, H. et al. The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells. Cancer Cell 27, 193-210 (2015).

first: Stephen

last: Wong

first: Xiang

first: Jianting

last: Sheng

first: Zhan

first: Ju Young

last: Ahn

first: Yuliang

last: Cao


title: Detection of statistically robust interactions from diverse RNA-DNA ligation data

status: Public on Mar 10 2026

city: Frankfurt

first: Simonida

last: Zehr

state: Hesse

address: Theodor-Stern-Kai 7

department: Institute for Cardiovascular Physiology

country: Germany

institute: Goethe University, Frankfurt am Main, Germany,

summary: Chromatin-localized RNAs play diverse roles in gene regulation and nuclear architecture. Mapping genome-wide RNA-DNA interactions is possible using a variety of molecular methods, including using bridging oligonucleotides to ligate RNA and DNA in proximity. While molecular methods have progressed, a robust computational method for calling biologically meaningful RNA-DNA interactions from these data is lacking. Herein, we present RADIAnT, a reads-to-interactions pipeline for analyzing RNA-DNA ligation data. RADIAnT calls interactions against a dataset-specific, unified background which considers RNA binding site-TSS distance and genomic region bias. By scaling the background with RNA abundance, RADIAnT is sensitive enough to detect specific interactions of lowly expressed transcripts, while remaining specific enough to discount false positive interactions of highly abundant RNAs. RADIAnT outperforms previously proposed methods in the accurate recall of genome-wide Malat1-DNA interactions, and in a use-case, was utilized to identify dynamic chromatin-associated RNAs in the physiologically- and pathlologically-relevant process of endothelial-to-mesenchymal transition, whose gene regulatory behaviour was validated experimentally.

overall_design: Total RNA-sequencing was performed on 3 HUVEC replicates, once in wildtype (endothelial phenotype), and once after siRNA-mediated knockdown of GAS5, MIR222hG and NUTM2BAS1, respectively.

first: Sandra

last: Seredinski

first: Katalin

last: Pálfi

first: James

middle: A

last: Oo

first: Emma

middle: C

last: Walsh

first: Alessandro

last: Bonetti

first: Matthias

middle: S

last: Leisegang

first: Ralf

middle: P

last: Brandes

first: Marcel

middle: H

last: Schulz

first: Timothy

last: Warwick


title: Early transcriptional divergence underlies cell fate bias in bovine embryos

city: Fuchu

first: Satoshi

last: Sugimura

state: Tokyo

address: 3-5-8 Saiwai-cho

country: Japan

institute: Tokyo Uiniversity of Agriculture and Technology

summary: We performed single blastomere RNA-seq on individual cells from 1-cell to 8-cell stage bovine embryos to investigate transcriptional heterogeneity during early embryonic development. A total of 90 blastomeres were collected from in vitro-produced embryos. The results provide insights into cell-to-cell variability during early cleavage stages in cattle.

overall_design: In vitro-produced bovine embryos at 1-cell, 2-cell, 4-cell, and 8-cell stages were individually disaggregated to isolate single blastomeres. RNA was extracted and sequenced using paired-end 150 bp reads on the Illumina NovaSeq 6000 platform. Transcript abundance was quantified using STAR and RSEM, and data were analyzed with PCA and clustering.

first: Hinata

last: Koyama

first: Daisuke

last: Mashiko

first: Masahiro

last: Kaneda

first: Atchalalt

last: Khurchabilig


title: Charting the transition from in vitro production through in vivo diversification of human glial progenitor cells

status: Public on Mar 09 2026

city: Rochester

first: Steven

last: Goldman

state: NY

address: 601 Elmwood Ave

department: Center for Translational Neuromedicine

institute: University of Rochester Medical Center

type: Genome binding/occupancy profiling by high throughput sequencing

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Single cell transcriptional profile of third instar larval wing discs in Drosophila using single cell RNA-seq (Chromium 10x)

city: Chicago

first: Maria

middle: Paula

last: Zappia

state: IL

address: 900 S Ashland Ave

department: Biochemistry and Molecular Genetics

institute: University of Illinos at Chicago

summary: Our study focuses on understanding the early transcriptional changes taking place during the divergence of the adult muscle precursors that give rise to indirect flight muscles and direct flight muscles in Drosophila. Here, we studied the functional relevance of Arginine Kinase in flight muscle development by depleting Argk expression specifically in the adult muscle precursors. We determined the transcriptional changes and perturbations in AMP cell identity upon Argk knockdown.

overall_design:
10X scRNA-seq on the single cell suspension from third instar larval wing discs (hinge and notum, pouch was manually removed during dissection).

UPDATE
[Jul-10-2026] The GSE138625_Annotated_Myoblasts_Barcodes.csv.gz and GSE138625_Annotated_Myoblasts.rds files were replaced.

first: Maxim

middle: V

last: Frolov

first: Abul

middle: B

last: Islam


title: Transcriptomic analyses of labial glands and gut tissue from two wax moths, Achroia grisella and Galleria mellonella

status: Public on Mar 08 2026

city: Acton

first: Gunjan

last: Pandey

address: Clunies Ross Street

department: Environment

country: Australia

institute: Commonwealth Scientific and Industrial Research Organisation

summary: Plastics are highly stable materials with widespread applications, but their resistance to degradation poses a significant environmental challenge, often resulting in accumulation in landfills or pollution in the form of microplastics. Biodegradation using insect larvae has recently emerged as a promising strategy to address this issue, though the molecular basis of plastic degradation in these organisms remains poorly understood due to limited genomic resources. In this study, we present a complete genome of the lesser wax moth, Achroia grisella, and tissue-specific RNA-Seq data of both the lesser and the greater wax moth, Galleria mellonella, two species known to consume various plastics. Our analyses reveal several highly expressed secretory enzymes in gut and labial tissues. Orthologous comparisons of differentially expressed genes also identified five enzymes (three hexamerins and two monooxygenases) from the lesser wax moth that have been shown or are predicted to have plastic-degrading potential in the greater wax moth. We also identified enzymes that may potentially be involved in polyethylene and polystyrene degradation based on their identities with known bacterial enzymes that have been experimentally validated and are involved in plastic degradation pathways. Together, these genomic and transcriptomic resources provide a foundation for understanding plastic degradation in wax moths and highlight candidate genes for future functional validation.

overall_design: RNA-Seq analysis of digestive tissue (gut, labial glands) of penultimate instar A. grisella larvae to identify candidate catabolic enzymes potentially capable of acting on long-chain hydrocarbons. Fat body was also sequenced and used as the reference tissue. Tissue from five individual specimen were collected and pooled for the whole gut and labial gland tissues whilst tissue from three individual specimen were collected and pooled for the fat body.

first: Reginald

last: Young

first: Khandaker

last: Ahmed

first: Leon

last: Court

first: Rahul

last: Rane

first: Tom


overall_design: RNA-Seq analysis of digestive tissue (gut, labial glands) of penultimate instar G. mellonella larvae to identify candidate catabolic enzymes potentially capable of acting on long-chain hydrocarbons. Fat body was also sequenced and used as the reference tissue. Tissue from five individual specimen were collected and pooled for the whole gut and labial gland tissues whilst tissue from three individual specimen were collected and pooled for the fat body.

last: Walsh


title: A Positive Feedback Loop Between TKT and c-Myc Drives TACE Resistance In Hepatocellular Carcinoma

status: Public on Mar 07 2026

city: Nantong

first: Yifu

last: Xiao

address: xisi Road

country: China

institute: Affiliated Hospital of Nantong University

summary: Hepatocellular carcinoma (HCC) often receives transarterial chemoembolization (TACE), yet clinical benefit is limited by resistance driven by ischemia-induced adaptations. This study explains how transketolase (TKT) in the pentose phosphate pathway (PPP) modulates HCC progression and TACE refractoriness, and clarifies its mechanistic connection to oncogenic signaling.

overall_design: We integrated transcriptomic screening with analyses of TACE patient specimens, and  performed  gain  and  loss  of  function  experiments  across  HCC  cell  lines. Functional assays, RNA-seq with pathway enrichment, western blotting, immunofluorescence,cycloheximide-chase and ubiquitination assays, and an orthotopic VX2 rabbit TACE model with imaging and immunohistochemistry were used.TKT emerged as a hub gene, was elevated in TACE-resistant patients, and promoted proliferation, migration, invasion, epithelial–mesenchymal transition, and apoptosis resistance.Mechanistically, TKT associates with RAF1, promoting phosphorylation of c-Raf at Ser338 and subsequent ERK activation, and stabilizes c-Myc by enhancing Ser62 phosphorylation and reducing ubiquitin-mediated degradation. Additionally, c-Myc enhances the transcriptional expression of TKT, creating a positive feedback loop between TKT and c-Myc.These findings identify a TKT/c-Myc positive feedback loop that underlies TACE resistance and HCC progression, nominating TKT as a biomarker of refractoriness and a therapeutic target to improve locoregional treatment outcomes.


title: Keratin 5 expression defines cancer-propagating cells that are sustained by a hierarchically related osteopontin-producing niche in high-grade serous ovarian carcinoma

status: Public on Mar 06 2026

city: Ithaca

first: Coulter

last: Ralston

address: 237 Tower Rd

department: Biomedical Engineering

institute: Cornell University

summary: High-grade serous carcinoma (HGSC) is the most common and aggressive form of ovarian cancer. Advanced HGSCs display marked cellular heterogeneity. A subset of tumor cells functions as cancer-propagating cells (CPCs, also referred to as cancer stem cells), which are highly tumorigenic and exhibit stem cell-associated properties, including self-renewal and chemoresistance. In contrast, a substantial fraction of HGSC cells is non-tumorigenic. The role of these non-cancer-propagating cells (non-CPCs) and their relationship to CPCs remain poorly understood. Here, we demonstrate that neoplastic cells expressing the intermediate filament protein keratin 5 (KRT5) represent bona fide CPCs. KRT5⁺ cells form cancer organoids over successive passages, are tumorigenic in serial dilution xenograft assays, and are resistant to the antineoplastic agents doxorubicin and cisplatin. Single-cell lineage-tracing experiments show that KRT5⁺ CPCs give rise to KRT5⁻ cells. KRT5⁺ and KRT5⁻ populations exhibit distinct gene expression profiles, with KRT5⁻ cells characterized by expression of SPP1, which encodes the secreted factor osteopontin (OPN). Treatment with OPN enhances HGSC organoid growth and chemoresistance, whereas SPP1 knockdown reverses these effects. Together, these findings support a model in which HGSC contains two hierarchically related cell populations: KRT5⁺, OPN-responsive CPCs and KRT5⁻, non-tumorigenic cells that form a niche producing OPN. Targeting pathways that sustain both stem-like tumor cells and their supportive niche may enable reduced dosing of highly toxic chemotherapeutic agents while enhancing therapeutic efficacy in HGSC.

overall_design: RNA-seq analysis to explore how the transcriptome of high-grade serous ovarian carcinoma cell line, SKOV3, after sorting the cells based on KRT5 positivity.

first: Mallikarjun

last: Bidarimath

middle: R

first: Ian

middle: M

last: Rose

first: Alexander

middle: Y

last: Nikitin


title: Multiome Profiling Reveals Astrocyte and Neuroendocrine Targets of Prenatal Acoustic Programming in Zebra Finch Embryos

city: Clemson

first: Prakrit

last: Subba

state: SC

address: 132 Long Hall, 230 Parkway Drive

department: Biological Sciences

institute: Clemson University

summary: Prenatal sensory experience can program offspring phenotypes, yet the cell-type-specific regulatory mechanisms remain poorly understood. In zebra finches (Taeniopygia guttata), parental heat call vocalizations program offspring for thermal environments. To identify the cellular and epigenetic targets of this acoustic programming, we performed single-nucleus multiome sequencing (joint snRNA-seq and snATAC-seq) on medial hypothalamic punches from embryonic day 13 (E13) zebra finch embryos exposed to heat call or control call playback from E9–E13. We profiled 55,950 nuclei across 49 cell clusters representing 13 cell types. Differential chromatin accessibility analysis revealed a striking enrichment of chromatin remodeling in astrocytes (204 of 236 differentially accessible peaks), with Heat Call exposure predominantly increasing chromatin accessibility. chromVAR motif enrichment identified NFIC and AP-1 family transcription factors as top differentially active motifs in heat call embryos. Weighted gene co-expression network analysis identified an astrocyte module (Astro-M7) positively associated with heat call exposure, enriched for Notch signaling components. Cicero co-accessibility analysis revealed 9,502 heat call-specific chromatin loops involving 3,891 unique regulatory elements, concentrated at gliogenic regulators including NFIA, HES-5-like, and DLL1. Pseudotemporal trajectory analysis showed accelerated astrocyte developmental progression in heat call embryos. Additionally, transthyretin (TTR) showed sexually dimorphic, playback-associated expression in paraventricular nucleus glutamatergic neurons. Together, these findings reveal an epigenetic priming mechanism by which prenatal acoustic cues accelerate astrocyte maturation and reshape neuroendocrine programs in the developing hypothalamus.

overall_design: Zebra finch (Taeniopygia guttata) eggs were exposed to heat call or control call playback from embryonic day 9 (E9) to embryonic day 13 (E13). At E13, medial hypothalamic punches were collected from embryos (n = 8 pools total; 4 heat call, 4 control; each pool comprised 5 hypothalamic tissue punches). Nuclei were isolated and processed using the 10x Chromium Single Cell Multiome ATAC + Gene Expression kit to obtain joint chromatin accessibility and gene expression profiles from the same single nuclei. Libraries were sequenced and aligned to the zebra finch reference genome (bTaeGut1.4.pri) using Cellranger-arc (v2.0.2). After quality control, 57,388 of 60,138 nuclei were retained for RNA-seq analysis and 70,720 of 76,730 nuclei were retained for ATAC-seq analysis. Joint multimodal clustering using Weighted Nearest Neighbor (WNN) analysis in Seurat/Signac identified 49 clusters representing 13 cell types across 55,950 nuclei.

first: Vijay

last: Shankar

first: Kaitlyn

last: Williams

first: Trudy

last: Mackay

first: Patrick

last: Freymuth

first: Natalie

last: Shay

first: Allison

last: Rees

first: Shannon

last: Liedl

first: Jonathan

last: Roberts

first: David

middle: F

last: Clayton

first: Julia

last: George


title: Impaired CD4+ T cell help through the CD40L-CD40 pathway contributes to reduced tumor control in males

city: St. Louis

first: Elise

last: Alspach

state: MO

address: 1100 South Grand Boulevard

department: MMI

institute: St. Louis University

summary: Sex-based differences in cancer incidence are incompletely understood, but potential roles for the immune system are beginning to emerge. CD4+ T cells play a central role in organizing antitumor immunity. In addition to cytokine production, CD40L expression on CD4+ T cell provides necessary helper signaling to dendritic cells that is required for the priming of cytotoxic tumor-specific CD8+ T cells. Despite these critical functions, the impact of biological sex on the CD4+ T cell response to cancer remains unknown. Here, we demonstrate that impaired immune-mediated tumor control in male compared to female mice is driven by disparate helper CD4+ T cell responses between the sexes. We find that CD40L expression is reduced on CD4+ T cells isolated from males via a mechanism predominantly driven by sex hormones, resulting in decreased CD40 signaling in dendritic cells within tumor-draining lymph nodes. These deficits resulted in decreased helper CD4+ T cell frequencies and impaired CD8+ T cell function within the male tumor microenvironment which could be rescued by targeting the CD40L-CD40 axis. Our findings identify a novel mechanism of CD4+ T cell-based sex differences in the immune response to cancer that impairs tumor control.

overall_design: MB49 tumors were harvested from male and female mice 14 days following transplant.

first: Katey

last: Hunt

first: Samantha

last: Cooke

first: Lindsey

last: Kuehm

first: Tyson

last: Lobb

first: Emily

last: Ebert

first: Smirthi

last: Beeram

first: Ryan

last: Teague

first: Michelle

last: Brennan

first: Melissa

last: Berrien-Elliott

first: Stephen

middle: T

last: Ferris


title: Impaired CD4+ T cell help through the CD40L-CD40 pathway contributes to reduced tumor control in males [MB49 tumor cells]

overall_design: MB49 tumor cells were cultured prior to being submitted for scRNA seq.


title: Translatome analysis reveals altered spinal astrocyte metabolism in acute and chronic pain

status: Public on Mar 19 2026

city: Palo Alto

first: Vivianne

middle: L.

last: Tawfik

state: CA

address: 3174 Porter Drive

department: Anesthesiology, Perioperative & Pain Medicine

institute: Stanford University

summary: Chronic pain affects an estimated 20% of people globally, but the mechanisms that differentiate acute pain from chronic pain are not well understood. Astrocytes regulate neuronal signaling in physiological conditions and can drive neuroinflammation in pain states, likely contributing to pain progression. It is therefore important to determine how astrocyte cellular and molecular pathways change in response to pain-inducing peripheral injury, and to identify critical timepoints of astrocyte involvement in pain progression. Here, we utilize translating ribosome affinity purification technology in a mouse model of complex regional pain syndrome to uncover the molecular signature of spinal astrocytes in early (acute) and late (chronic) post-injury phases. We find that astrocytes exhibit a temporally distinct translatomic signature, with the most significant gene expression changes occurring early after injury. We further identify astrocyte lipid metabolism and oxidative phosphorylation as key dysregulated pathways after injury, and discover that orlistat, a clinically approved weight loss drug that reduces systemic lipid load, prevents the development of chronic pain in CRPS mice. Overall, this work highlights the importance of astrocyte lipid metabolism in pain pathophysiology and suggests that targeting this pathway may have therapeutic potential.

overall_design: Using Aldh1l1-CreER x Rpl22-HA mice, spinal cord astrocyte ribosomes were tagged with an HA protein. Tagged ribosomes were then immunoprecipitated using anti-HA antibody and magnetic coated beads. Immunoprecipitated samples were named "Trap" samples, and consisted of astrocytic mRNA only. Respective control samples were named "Input" and consisted of astrocytic mRNA and mRNA from all other cell types in the tissue. Both Trap and Input samples were colleced at 3-, 5-, and 7-weeks post-injury in a mouse model of Complex Regional Pain Syndrome or were collected from uninjured control animals. 3 replicates per group per sex were collected.

first: Janelle

last: Siliezar-Doyle

first: Richard

middle: K

last: Perez

first: Emma

last: Stauffenberg

first: Amy

last: Nippert

middle: L


title: Mettl8 programs Tcf1+CXCR5+ T cells in autoimmune disease and tumor by mediating Tcf1 mRNA m3C modification and Tcf1-bound chromatin loops

first: Jia

last: Li

state: Texas

address: 2121 W HOLCOMBE BLVD

department: CEDP

institute: Guangzhou Medical University

summary: In the tumor microenvironment (TME), the active tertiary lymphoid structure (TLS) plays a crucial role in fostering the reactivation of naïve or memory cells, leading to the expansion of effector cells. However, an excessive reinvigoration of T cells can result in autoimmune-like diseases, such as those observed in immune checkpoint blockade (ICB) therapy. Here, we have identified that the gene encoding RNA methyltransferase Mettl8 is highly expressed in inflammatory CD4+ CXCL13+ TFH cells of autoimmune patients. Surprisingly, the genetic deletion of Mettl8 in mice resulted in a reduced autoimmune phenotype in helper CD4 cells and slowed tumor growth through increased activation/effector response in CD8+ T cells. Mechanistically, Mettl8 is found to imprint m3C modification, stabilizing Tcf1 mRNA, and simultaneously interacts with Tcf1 protein to co-bind specific genome loops for genomic reorganization, as revealed by Hi-C analysis. These findings suggest that targeting Mettl8 promotes antitumor immunity while preventing the occurrence of autoimmune diseases. Notably, pharmacological inhibition of sumoylation-stabilizing Mettl8 protein has shown efficacy in compromising autoimmune CXCL13+ TFH specialization and function. In conclusion, these findings underscore the dual regulatory elements of the Mettl8-Tcf1 complex as a promising target for tumor immunotherapy, offering protection against autoimmune diseases.

overall_design: To investigate whether Mettl8 deficiency causes alterations in Tcf1 binding sites and chromatin accessiblity, we performed Mettl8 and Tcf1 CUT&Tag, and ATAC-seq in WT and Mettl8 KO CD8+ T cells.Given that Tcf1 regulates genomic organization to maintain CD8+ T cell identity, we next examined whether Mettl8 deficiency disrupts Tcf1-mediated 3D genome organization by HiC.To comprehensively understand the impact of Mettl8 deficiency on CD8+ T cells, we conducted RNA sequencing on sorted tumor-infiltrating CD8+ T cells. Considering the heterogeneous expression of these markers across T cell subsets, we further performed RNA sequencing on sorted Ly108+ Tim3− TPEX, Tim3+ CX3CR1+ Ly108− Int-TEX, and Tim3+ CX3CR1− Ly108− TEX subsets. To investigate the molecular mechanism of Mettl8 regulating TPEX cell transition, we conducted m3C-seq and Mettl8-RIP-seq using sorted tumor-infiltrating CD8+ T cells.


title: Inhibition of circulating glycocholic acid-regulated signaling potentiates immune checkpoint therapy in colorectal cancer immune evasion and resistance to anti PD1 immunotherapy by suppressing FBXW7 mediated CD73 degradation

status: Public on Mar 03 2026

city: Shanghai

first: Senlin

last: Zhao

address: 270 Dong An Road

department: Colorectal Surgery

institute: Cancer Hospital, Fudan University

summary: Serum bile acids (BAs) (1) are an important risk factor for the initiation and progression of cancer, but their roles in colorectal cancer (CRC) remain largely unknown. The present study showed that glycocholic acid (GCA), a primary BA, was highly accumulated in the serum of patients with CRC. In a mouse model of CRC, GCA diet promoted programmed death-ligand 1 (PD-L1) expression in tumors, which attenuated CD8+ T cell-mediated antitumor responses in the tumor microenvironment (TME) (2), and promoted the occurrence and development of CRC. Increased PD-L1 expression was caused by the reduction in activity of the BA receptor farnesoid X receptor (FXR). Mechanistically, FXR acted as transcriptional repressor for the transcription factor SRY-box transcription factor 14 (SOX14), and suppressed the palmitoylation and stabilization of PD-L1 by inhibiting the SOX14-mediated expression of zinc finger DHHC-type palmitoyl transferase 9 (DHHC9). Notably, genetically silencing SOX14 and DHHC9 in cancer cells or administering an FXR agonist synergized with anti-PD-1 therapy, leading to reduced tumor growth in GCA-fed mice. Together, the present findings reveal a previously unrecognized mechanism of BA in remodeling the TME to mediate CRC resistance to immunotherapy, which may have clinical implications for developing immunotherapy strategies for patients with CRC.

overall_design: 6-week-old C57BL/6Jmice were injected subcutaneously into the right flank with 1.0x106 MC38 cells, then  were treated with ot without GW4064 twice per week after 6 days.  Then, tumors  were  sheared and isolated into single-cell suspensions.  Goblet cells were considered as a homogeneous population and analyzed using scRNAseq.

first: Jing

last: Zhang

first: Yushuai

last: Mi

first: Zijuan

last: Hu

first: Xinyang

last: Zhong

first: Ye

last: Xu

first: Sanjun

last: Cai

first: Xinxiang

first: Ping

last: Wei

first: WanJun

last: Chen

first: Dawei


title: Novel Stem Cell Model Uncovers Macrophage-Mediated Antiviral Immunity and Repair in Human Type 2 Alveolar Epithelial Cells

status: Public on Mar 04 2026

city: Parkville

first: Michael

last: See

state: VIC

address: Royal Children's Hospital, 50 Flemington Rd

institute: MCRI

summary: The lung alveoli are constantly exposed to inhaled pathogens and inorganic hazards, relying on robust defence mechanisms to maintain homeostasis. Alveolar macrophages and type 2 alveolar epithelial cells (AT2s) collaborate to orchestrate protection. Compromised defence can dysregulate immunity and repair, leading to acute and chronic respiratory diseases. To better understand these processes and drive therapeutic discovery, human model systems that capture key cell interactions are essential. Here, we develop the first induced pluripotent stem cell (iPSC)-derived platform that integrates AT2 cells and macrophages in an air-liquid interface. Coculture enhanced AT2-specific gene expression and lipid synthesis, while macrophages actively metabolised surfactant. iPSC-derived AT2s supported macrophage survival by producing M-CSF, promoting an alveolar macrophage-like phenotype. Additionally, macrophages played a crucial role in modulating proinflammatory signalling, enhancing antiviral immunity, and restricting viral replication during respiratory infections. Furthermore, we identify a role for iPSC-derived macrophages in epithelial repair, a process disrupted by VEGF signalling. We present an iPSC-derived platform to study AT2-macrophage interactions in homeostasis, infection, and repair, offering valuable insights into their roles in respiratory disease initiation and progression.

overall_design: Monocultured iAT2s and iMacs, iAT2-iMac co-cultures, as well as RSV infected iAT2s, iMacs and iAT2-iMac cocultures were captured and sequences for scRNA-seq using 10X Flex workflow (10X-1000475) at 48 hours post infection.

first: Declan

last: Turner

first: Hannah

last: Baric

first: Katelyn

last: Patatsos

first: Sahel

last: Amoozadeh

first: Kathleen

last: Strumila

first: Jack

last: Murphy

first: Liam

last: Gubbels

first: Melanie

last: Neeland

first: Shivanthan

last: Shanthikumar

first: Sarah

last: Londrigan

first: Mirana

last: Ramialison

first: Fernando

last: Rossello

first: Ed

last: Stanley

first: Rhiannon

last: Werder


title: A Single-Cell and Spatial 3D-Epigenomic Atlas of Developing Human Basal Ganglia and Inhibitory Neurons

status: Public on Mar 02 2026

city: Los Angeles

first: Chongyuan

last: Luo

address: 695 Charles E Young Drive South

department: Human Genetics

institute: University of California Los Angeles

summary: During human brain development, the basal ganglia arise from transient progenitor zones in the ventral telencephalon—the lateral, medial, and caudal ganglionic eminences (LGE, MGE, and CGE, respectively). These regions generate inhibitory projection neurons and interneurons that populate diverse brain regions, yet the developmental programs underlying this cellular diversity remain incompletely understood. This study aims to elucidate the epigenomic and 3D-genomic dynamics involved in the specification and maturation of GEs and GE-derived neurons, using single-nucleus methyl-3C sequencing (snm3C-seq), chromatin+RNA single-molecule imaging, and highly-multiplexed spatial transcriptomics. The multi-modal data support a heterogeneous temporal progression across GEs, with LGE showing declining neurogenic activity in mid-gestation and CGE exhibiting prolonged activity in infancy. We reconstructed the regulatory programs of MSN subtype specification and revealed an unusually synchronized maturation of the 3D-Epigenome across individual MSN cells. The differentiation of neurons and glial cells is associated with permanent Short-range Enriched (SE) and Long-range Enriched (LE) chromatin conformation, respectively 1. We found a reversible shift toward LE in projection neurons in early infancy, and a temporary SE conformation during transition between oligodendrocyte progenitors (OPCs) and oligodendrocytes (ODCs). Mapping genetic risk for neuropsychiatric disease to single brain cells highlights the critical role of MSNs in infancy. Our study provides a comprehensive 3D-Epigenomic map of human brain cell development in the basal ganglia and reveals highly complex and lineage-specific 3D genomic dynamics.

overall_design:
The study generated 155,225 new snm3C-seq profiles sampled from nine developing brains.  The dissected brain regions include the lateral ganglionic eminence (LGE), medial ganglionic eminence (MGE), caudal ganglionic eminence (CGE), putamen (Pu), caudate (Ca), globus pallidus (GP), ventricular zone (VZ), dorsallateral prefrontal (DFC), ventrolateral prefrontal (VFC), frontal (FCx), orbital frontal (OFC), temporal (TCx), cingulate (CCx), insular (ICx) cortices, postcentral gyrus (PoCG), and the hippocampus (HIP). Fastq files for the snm3C-seq data are available through the NeMO archive under accession nemo:dat-n5emc24 (https://assets.nemoarchive.org/dat-n5emc24).

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NeMO archive (https://assets.nemoarchive.org/dat-n5emc24) per NIH requirement
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first: Matthew

middle: G

last: Heffel

first: Heng

last: Xu

first: Oier

last: Pastor-Alonso

first: Xinzhe

last: Li

first: Rayyan

middle: I

last: Ghoor

first: Runjia

first: Yi

last: Zhang

first: Joonho

last: Kum

first: Mohammad

last: Baig

first: Jon

last: Paino

first: Min Jen

last: Tsai

first: Zachary

last: von Behren

first: Mohini

last: Bhade

first: Siqian

first: Kadellyn

last: Sandoval

first: Jessica

last: Scholes

first: Felicia

last: Codrea

first: Jeffrey

last: Calimlim

first: Emma

last: Liao

first: Gwyneth

last: Leung

first: Jaeyeon

last: Kim

first: Eleazar

last: Eskin

first: Jonathan

last: Flint

first: Bogdan

last: Pasaniuc

first: Eran

last: Mukamel

first: Jason

last: Ernst

first: Mercedes

last: Parades


title: Competition between commensal protists shapes gut mucosal immunity in mice

city: Madison

first: Marienela

middle: Yaritza

last: Heredia

state: WI

address: 1550 Linden Drive

department: Medical Microbiology & Immunology

institute: University of Wisconsin-Madison

summary: Intestinal protists are emerging as key modulators of host immunity and microbial ecology, yet their roles remain poorly defined. Here, we investigated the role of two distinct protists, the amoeba Entamoeba muris, and the parabasalid, Tritrichomonas, to determine how they shape gut immunity in vivo individually and together. Unlike the well-characterized inducer of type 2 immunity, Tritrichomonas, which activates the tuft cell–IL-25–ILC2 circuit in the small intestine, E. muris failed to elicit robust immune responses in the intestine or colon. However, introduction of E. muris into mice naturally colonized by Tritrichomonas spp., or co-infection with E. muris and Tritrichomonas spp. suppressed the Tritrichomonas-induced type-2 response in the small intestine. Fecal and cecal qPCR suggest that E. muris may outcompete Tritrichomonas spp., with reduced protist loads in the cecum and possibly diminished succinate-driven tuft cell activation. We also identified sex-specific differences in the intestinal response to primary Tritrichomonas spp. colonization which have not previously been described. These findings reveal that E. muris can dampen existing type-2 immune circuits without triggering overt inflammation, underscoring its role as an immunomodulatory agent. This work provides a framework for understanding how commensal protists interact within the gut ecosystem and shape mucosal immunity in the absence of pathogenicity.

overall_design: Bulk RNA-seq profiling of distal small intestine and proximal colon tissue segments harvested from uninfected mice, E. muris-infected mice, Tritrichomonas-infected mice, or mice co-infected with both E. muris and Tritrichomonas. All mice are of the C57BL/6J background. Tissues were harvested at 28 dpi.

first: Paul

middle: A

last: Kuehnert

first: Kylie

last: March

first: Laura

middle: J

last: Knoll

first: Claire

middle: E

last: O'Leary


title: Brassinosteroids mediate proper coordination of sepal elongation [Spatial Transcriptomics]

first: Byron

last: Rusnak

email: bzr5@cornell.edu, ahr75@cornell.edu

department: Plant Biology

summary: Arabidopsis sepals must grow in a coordinated and robust fashion to a consistent size and shape to close and protect the developing flower bud. To understand how this robust coordination occurs, we use the loss of robustness mutant development related myb-like1 (drmy1), which exhibits variable sepal initiation and growth, causing failure of the sepals to close the flower bud. Specifically, drmy1 has overgrown outer (abaxial) sepals and undergrown inner (adaxial) sepals, leading to a large discrepancy in the sizes of different sepals within individual flower buds. Using single cell and spatial RNA-seq, we found changes in expression of key genes related to brassinosteroid (BR) signaling in drmy1, particularly in cell types important to young flower bud development such as epidermal cells, boundary cells, and meristematic cells. Confocal imaging of a BRI1-EMS-SUPPRESSOR1 (BES1) ratiometric reporter confirms that BR signaling is upregulated and more variable in young drmy1 sepals. Subsequently, we found that altering BR signaling in drmy1 by crossing with BR mutants or adding brassinolide (a potent brassinosteroid) or brassinazole (a brassinosteroid biosynthesis inhibitor) can partially rescue this elongation defect by differentially altering the relative growth of the inner and outer sepals. Increasing BR signaling rescues by increasing the growth of the inner sepal but not the outer sepal, while decreasing BR signaling rescues by decreasing the growth of the outer sepal but not the inner sepal. These results suggest that brassinosteroids mediate the robust coordination of the growth rates between inner and outer sepals during early development, ensuring proper flower bud closure.

overall_design: 108 hours after induction with dexamethasone, WT and drmy1 in the ap1cal 35S::AP1-GR background was harvested by cutting off the cauliflower-like clusters of flower buds and embedded in OCT compound and flash frozen in liquid nitrogen cooled isopentane (2-methylbutane). 10 micron thick cryosections were then taken on a cryostat and placed on 10x Visium spatial transcriptomic capture areas

last: Rusank

first: Lilijana

last: Oliver

first: Kyle

last: Procopio

first: Adrienne

last: Roeder


title: SCD1 and SCD5 Modulate PARP-Dependent DNA Repair via Fatty Acid Desaturation in Glioblastoma

city: Boston

first: Hayk

last: Mnatsakanyan

state: MA

address: 149 13th Street Charlestown

department: Neurology

institute: Massachusetts General Hospital

summary: Glioblastoma (GBM) relies on fatty acid metabolism to sustain its aggressive growth. While the role of stearoyl-CoA desaturase-1 (SCD1) in GBM is established, the function of its brain-enriched isoform, SCD5, remains unexplored. Here, we demonstrate that SCD5 is essential for glioblastoma stem cell (GSC) maintenance and genomic stability, with elevated expression in GSCs that declines upon differentiation, underscoring its role in tumor initiation. Through shotgun lipidomics, 13C metabolic flux analysis, and functional genomics, we reveal that SCD1 and SCD5 play non-redundant roles in fatty acid desaturation, with SCD5 preferentially desaturating C18:0 and uniquely contributing to sphingolipid remodeling. Genetic silencing of either isoform disrupts cell cycle progression, impairs DNA damage repair, and reduces GSC viability, while SCD5 knockdown significantly extends survival in orthotopic GBM models. Mechanistically, loss of SCD activity or saturated fatty acid accumulation triggers PARP1 hyperactivation and subsequent degradation, depleting RAD51 to compromise homologous recombination and induce parthanatos. These findings uncover a lipid-mediated vulnerability in GBM, linking fatty acid desaturation to PARP1-dependent genome integrity. Targeting SCD5 may offer a novel therapeutic strategy to eliminate therapy-resistant GSCs and enhance the efficacy of genotoxic or immunotherapeutic interventions.

overall_design: RNA-seq profile of glioma stem cells (GSCs; Mayo120) after 4 days of control, stearoyl-CoA desaturase (SCD1), or SCD5 knockdown.

first: Christian E.

last: Badr


title: Single-cell transcriptomic profileing of IMR-90 SV40-T cells expressing wild-type, E76K or E76R H2B

city: La Jolla

first: Peter

middle: D.

last: Adams

address: 10901 North Torrey Pines Road

department: Cancer Genome and Epigenetics Program

institute: Sanford Burnham Prebys Medical Discovery Institute

summary: Nucleosomes are the minimal repeating units of chromatin. Their dynamic assembly and disassembly underpins chromatin organization and genome regulation. However, how intrinsic nucleosome stability contributes to higher-level yet fundamental cellular and organismal properties—such as preservation of cell identity, lineage specification, stress resilience and healthy aging—remains unclear. To address this, we tested the impact of intrinsic nucleosome instability across multiple cell, tissue and organismal models by introducing histone mutants that weaken histone–histone interactions. Despite no overt effects on global chromatin accessibility, DNA damage, steady-state proliferation or cell viability, nucleosome instability impaired lineage-specific gene expression programs, altered lineage specification and activated intrinsic inflammatory and stress pathways in a manner reminiscent of aging in mouse tissues and human cells. Consistently, in Caenorhabditis elegans and Drosophila melanogaster, nucleosome instability accelerated the onset of age-associated transcriptional alterations and functional decline in Caenorhabditis elegans and Drosophila melanogaster, and . At the cellular level, nucleosome instability also heightened cellular sensitivity vulnerability to exogenous perturbations—including environmental, epigenetic and mitotic stress—in human cells and Saccharomyces cerevisiaeyeast.  These cross-species findings identify nucleosome stability as an evolutionarily conserved epigenetic safeguard that preserves cell identity and stress resilience, sustaining organismal function and longevity.

overall_design: IMR-90 SV40-T immortalized human fibroblasts were transduced with lentiviruses expressing wild-type or mutant H2B constructs (E76K, E76R). Single-cell suspensions were processed using the Chromium platform at the UC San Diego Center for Epigenomics. Libraries were sequenced and analyzed to identify gene expression changes and cluster-specific marker genes.

first: Hiroshi

last: Tanaka

first: Xue

last: Lei

middle: D


title: Chromatin accessibility profiling of IMR-90 SV40-T cells expressing wild-type and mutant H2B

overall_design: IMR-90 SV40-T immortalized human fibroblasts were transduced with lentiviral vectors expressing wild-type or mutant H2B construct. ATAC-seq libraries were prepared using the Active Motif ATAC-seq Kit and sequenced on NovaSeq 6000. Peaks were called using MACS2, quantified with featureCounts and analyzed for differential accessibility using DESeq2.


title: Bulk mRNA-seq analysis of Caenorhabditis elegans expressing wild-type and mutant H2B

overall_design: Worms expressing either wild-type or E73R mutant H2B (his-41) were collected at three time points post-adulthood (day 1, day 3, and day 10). Total RNA was isolated, sequenced and analyzed to identify gene expression changes associated with the H2B mutation and aging.

first: Michael

last: Petrascheck


title: Bulk mRNA-seq analysis of IMR-90 SV40-T cells expressing wild-type and mutant H2B

overall_design: IMR-90 SV40-T immortalized human fibroblasts were transduced with lentiviruses expressing wild-type or mutant H2B constructs. Total RNA was isolated, sequenced and analyzed to identify gene expression changes.


title: Bulk mRNA-seq analysis of mouse hematopoietic stem and progenitor cells expressing wild-type and mutant H2B during myeloid and megakaryocyte/erythroid differentiation

overall_design: Mouse hematopoietic stem and progenitor cells (HSPCs) were transduced with MSCV retroviral vector expressing wild-type or mutant H2B. The cells were subjected to differentiation into myeloid and megakaryocyte/erythroid lineages using MethoCult GF M3434 supplemented with 20 ng/ml mouse FLT3L and 50 ng/ml mouse TPO. After 9 days, cells were collected, and total RNA was isolated, sequenced and analyzed to identify gene expression changes.


title: IL-17–Driven Tumor Cell–Intrinsic Inflammatory Programming Creates an Immunotherapy-Permissive Microenvironment [scRNA-Seq]

status: Public on Mar 01 2026

city: Sakai

first: Kosuke

last: Murakami

state: Osaka

address: 1-14-1, Miharadai, Minami-ku

institute: Kindai University

summary: Ovarian clear cell carcinoma (OCCC) is a chemoresistant subtype of ovarian cancer with limited effective therapeutic options. Although immune checkpoint inhibitors (ICIs) have shown little benefit in unselected ovarian cancer populations, clinical activity observed in a subset of OCCC patients suggests the presence of a histotype-specific immune vulnerability that remains poorly defined. To elucidate this biology, we integrated transcriptomic analyses from multiple independent human OCCC cohorts with immunohistochemical profiling and mechanistic studies using an immunocompetent syngeneic OCCC mouse model. Tumor cell–intrinsic and microenvironmental responses to IL-17 were investigated through in vitro stimulation assays, in vivo IL-17 administration, single-cell RNA sequencing of tumor-infiltrating T cells, and immune checkpoint blockade in a Th17-biased partial chimera model. OCCC was characterized as an IL-6–high tumor entity with a globally immune-sparse but CD4⁺ T-cell–skewed tumor immune microenvironment. Transcriptomic analyses identified a Th17-associated program marked by elevated RORC expression in a subset of tumors. Across large clinical cohorts, an IL17A^high subset demonstrated a T cell–inflamed gene expression profile independent of microsatellite instability and tumor mutational burden; however, this phenotype was not associated with survival in untreated disease. Mechanistically, IL-17 directly activated NF-κB–dependent inflammatory programs in OCCC tumor cells, inducing cytokines involved in T-cell recruitment and activation. In vivo, IL-17 remodeled the immune microenvironment, increasing infiltration and activation of both CD4⁺ and CD8⁺ T cells. Single-cell profiling further revealed expansion of Th17/Tfh-like CD4⁺ T cells and cytotoxic, non-terminally exhausted CD8⁺ T cells. Consistent with these findings, anti–PD-L1 therapy significantly improved survival exclusively in Th17-biased partial chimera mice. Collectively, these results demonstrate that a Th17-biased, IL-17–responsive immune contexture in OCCC engages tumor cell–intrinsic NF-κB inflammatory signaling to prime antitumor T-cell states and enable checkpoint blockade efficacy. This immune biology is predictive rather than prognostic, supporting a biomarker-driven immunotherapy strategy for OCCC within otherwise ICI-refractory ovarian cancer.

overall_design: Tumor tissues were collected from syngeneic murine ovarian clear cell carcinoma models established in immunocompetent mice. In selected experiments, tumors were generated under IL-17 or control conditions. Single-cell suspensions were prepared from excised tumors and processed for single-cell RNA sequencing using the BD platform. The study aimed to determine how an IL-17–enriched tumor microenvironment shapes immune cell infiltration, activation states, and immune checkpoint expression. Comparative analyses were performed between IL-17–exposed and control tumors.

first: Shiki

last: Takamura

first: Chiho

last: Miyagawa

first: Kazuhiro

last: Kakimi

first: Noriomi

last: Matsumura


title: Alterations in single-cell transcriptomic levels and cellular localisation of hnRNP proteins in Frontotemporal Lobar Degeneration

city: London

first: Yazead

last: Buhidma

state: London

address: 1 Wakefield Street

department: Department of Neurodegenerative Diseases

country: United Kingdom

institute: University College London

summary: Frontotemporal dementia (FTD) is a neurodegenerative disorder with a strong heritable component. Frontotemporal lobar degeneration (FTLD) refers to the pathological changes seen in FTD, characterised by atrophy of the frontal and temporal lobes and the presence of abnormal protein inclusions. In the case of FTLD with hyperphosphorylated TDP-43 positive inclusions (FTLD-TDP), five pathological  subtypes (A, B, C, D, and E) are observed based on the types and distribution of inclusions found in the brain. In all subtypes, there tends to be a large variability in the amount of pathological inclusions observed between cases, with limited correlation to clinical manifestations. TDP-43 is an RNA binding protein belonging to the heterogeneous nuclear ribonucleoprotein (hnRNP) family which along with other hnRNPs modulates multiple aspects of RNA processing. HnRNPs other than TDP-43 have been implicated in several neurological diseases, including ALS, FTLD-TDP, FTLD-FUS and Alzheimer's disease. Multiple hnRNPs have been found in pathological inclusions in specific subtypes of FTLD-TDP, suggesting potential roles in the disease process. The role of the hnRNP network in FTLD disease pathogenesis has not yet been investigated. This study aimed to comprehensively evaluate the presence and expression of hnRNP proteins in two pathological subtypes of sporadic FTLD-TDP (A and C) as well as the genetic form FTLD-TDP A C9orf72 using immunohistochemistry and gene expression analysis by single cell RNA-sequencing. We sought to determine whether hnRNPs exhibited aberrant expression at the protein and transcript level in FTLD cases with TDP-43 pathology.

overall_design: Nuclei were isolated from frozen frontal cortex grey matter from 3 FTLD-TDPA, 3 TDPA-C9, and 5 TDPC, and 5 healthy controls. Tissue was transferred directly onto ice-cold sucrose buffer and homogenised by hand. The homogenate was layered on top of a sucrose cushion and nuclei were recovered after centrifugation. Nuclei were resuspended in PBS containing BSA (to prevent clumping) and RNase inhibitors, counted and diluted to 1,000 nuclei/μl. Sequencing libraries were prepared using the “single cell 3’ library kit v3” with the Chromium instrument (10X Genomics). Aiming to obtain libraries for ~5,000 independent nuclei per sample. Libraries were sequenced on an Illumina NovaSeq6000 instrument (UCL Genomics), to an average of at least 100,000 reads/nucleus. Raw sequencing data were processed through the software CellRanger (10X Genomics) to assign each transcript read to its respective nucleus, we performed alignment to the transcriptome, counting reads, and processing of the unique molecular identifier tag to reduce PCR bias. The resulting gene count table was analysed using the Seurat package (version 4.4). Quality control was performed to remove low-quality cells based on the number of detected genes and unique molecular identifiers (UMIs). Cells with an unusually high number of UMIs, suggesting potential doublet events, were also excluded using scDblFinder. Using SCTransform, gene expression data were normalised to adjust for differences in sequencing depth between cells and scaled to correct for cell-to-cell variation in total UMI count. Data were also normalised to remove confounding sources of variation such as mitochondrial mapping percentage, post-mortem delay, age of death, and batch number.

first: Tammaryn

last: Lashley

first: Ariana

last: Gatt


title: CXCL16-driven CD4+ T cells orchestrate immunosurveillance against MHC-I-deficient tumors

first: Yunyi

last: Zhou

address: 1954 Huashan Road, Xuhui District

institute: Shanghai Jiao Tong University

summary: MHC-I loss is a prevalent mechanism for immune evasion and resistance to immunotherapy. However, the mechanisms by which MHC-I loss shapes the tumor microenvironment (TME) and influences the interactions between MHC-I-deficient tumors and immune cells, ultimately affecting tumor growth, remain largely unknown. Here, we found that MHC-I/B2M loss increased tumor growth rates in the MC38, AKR and LLC1 tumor models, but surprisingly led to regression of Hepa1-6 tumors. The effect of MHC-I/B2M loss on tumor growth was associated with the changes in immune infiltrates. CD4+ T cell, NK cells and macrophages were required to suppress the growth of MHC-I-deficient Hepa1-6 tumors, with CD4+ T cells appearing essential for maintaining of the tumoricidal phenotype of monocytes/macrophages and for recruiting NK cells and monocytes/macrophages. Moreover, the differential infiltration of CD4+ T cells was attributed to the upregulation of CXCL16 expression in Hepa1-6 upon loss of MHC-I/B2M, and the downregulation of CXCL16 due to MHC-I deficiency in other tumor models. CXCL16 exhibited a potent antitumor effect on MHC-I-deficient tumors by recruiting CD4+ T cells. In summary, CXCL16-driven CD4+ T cells are central regulators of antitumor immunity against MHC-I-deficient tumors.

overall_design: To investigate the mechanisms of MHC-I loss effecting tumor growth and tumor microenvironment, we established 4 MHC-I-deficient tumor cell lines (MC38, AKR, LLC1, and Hepa1-6) in which B2m has been knocked out by sgRNA. The non-targeting sgRNA was used for control. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 paired different cell lines.

first: Ping

last: Chen

first: Zhixue

last: Wang

first: Liming

last: Gui

first: Zhengheng

last: Zheng

first: Weiqiang

last: Gao

first: Bin

last: Ma


title: Small-Molecule Conversion of Neural Crest Cells to Corneal Endothelial Cells for Endothelial Regeneration

status: Public on Feb 28 2026

city: Wenzhou

first: zhengbiao

last: zhu

state: Zhejiang

address: Ouhai District

department: The Affiliated Eye Hospital of Wenzhou Medical University

institute: Wenzhou Medical University

summary: Purpose: Corneal endothelial dysfunction leads to irreversible blindness, yet treatment remains constrained by a global shortage of donor tissue. This study aimed to develop a donor-independent strategy for generating functional corneal endothelial cells (CECs) by reprogramming murine neural crest cells (NCCs) through pharmacological inhibition of TGF-β signaling. Methods: NCCs were genetically labeled and isolated from E13.5 Wnt1-Cre;Rosa26-LSL-tdTomato mouse embryos by fluorescence-activated cell sorting. Sorted NCCs were treated with the selective TGF-β inhibitor SB431542 to induce conversion into induced corneal endothelial–like cells (iCECs). Cell identity was validated by immunofluorescence, flow cytometry, wound-healing and endocytic uptake assays, and bulk RNA sequencing with comparison to primary CECs and NCCs. Therapeutic efficacy was assessed by transplanting iCECs into a rabbit model of corneal endothelial dysfunction induced by descemetorhexis. Results: SB431542 treatment efficiently converted NCCs into polygonal, cobblestone-like iCECs that expressed canonical CEC markers (ZO-1, Na⁺/K⁺-ATPase, AQP1, Laminin) while silencing neural crest genes. Approximately 85% of iCECs were Ki67-positive, and cells achieved complete wound closure within 24 hours. Transcriptomic profiling confirmed that iCECs closely resembled primary CECs and were clearly distinct from NCCs. Following transplantation, iCECs reconstituted a confluent endothelial monolayer, normalized central corneal thickness, and restored corneal transparency by Day 35, whereas untreated controls remained opaque. Conclusions: Targeted TGF-β inhibition enables efficient lineage conversion of NCCs into functional corneal endothelial–like cells with robust proliferative capacity and in vivo therapeutic efficacy. This pharmacologically defined strategy provides a scalable, donor-independent cell source and offers a promising therapeutic approach for corneal endothelial diseases.

overall_design: RNA-Seq profiles of E13.5 mouse primary neural crest cells (NCCs), corneal endothelial cells induced by TGF-β inhibitor SB431542 (iCECs), and primary corneal endothelial cells.

first: Yunfen

last: Li

first: Nanxi

last: Wu

first: Di

last: Cao

first: Liya

first: JiaHang

first: Miyao

last: Zhu

first: Wencan

first: Yuedan

last: Fan

first: Shaohui

last: Pan


title: Effect of  Rimegepant treatment on gene expression  in the trigeminal ganglion of mice on the tumor-transplanted side.

first: mingtao

address: 180 Fenglin Road, Xuhui District, Shanghai

institute: Zhongshan Hospital, Fudan University

summary: The trigeminal nerve is primarily responsible for facial sensation and exhibits the highest expression of CGRP.  Here, we explored the impact of Rimegepant on the transcriptome of the trigeminal ganglion in mice and found that the transcription profiles changed significantly following treatment compared to the control group.  Following Rimegepant administration, we observed a significant downregulation of innate immune-related items within the trigeminal ganglia, as well as functional items directly associated with pain perception and calcium signaling pathways.The activation of  innated immune within the trigeminal ganglia is known to enhance nociceptive responses, which were also directly linked to the activation of calcium signaling pathways.  These results suggest that Rimegepant alleviates OSCC-related pain by mitigating the inflammatory condition within the trigeminal ganglion. We then categorized the genes enriched in these functional groups.  Genes that promote the proliferation and differentiation of innate immune cells, and those related to the expression of proinflammatory mediators, were significantly downregulated, while those associated with anti-inflammatory functions were significantly upregulated.  Additionally, genes from various chemokine receptor families and ion channel genes linked to neuronal activity were significantly downregulated.  Collectively, these results suggest that CGRP influences OSCC-related pain by modulating the innate immune status of the trigeminal nerve.

overall_design: To investigate the mechanism of Rimegepant on OSCC-related pain,  we established unilateral tongue orthotopic transplantation modelson BALB/c nude mice which were randomly divided into an experimental group and a control group (n=3 in each group). In the experimental group, Rimegepant was intraperitoneally injected every 24 h for 4 consecutive days, starting from the 5th day after tumor inoculation. The control group received an equal volume of physiological saline. After the final drug treatment, both groups of mice were euthanized, with the trigeminal ganglia on the side of the transplantation tumor carefully isolated.

first: Mingtao

first: Yibo

last: Guo

first: Yu

last: Zhang


title: Identification of CD74-positive antigen presenting glioma cells in primary human tumors and murine models of NF1 high-grade glioma

city: Philadelphia

first: Thomas

last: De Raedt

state: PA

address: 3501 Civic Center boulevard CTRB 4028

institute: CHOP

summary: High-grade gliomas (HGG) arising in the context of Neurofibromatosis type 1 (NF1) present significant therapeutic challenges. To better understand the tumor microenvironment and immune interactions in these tumors, we developed and validated an immunocompetent murine allograft model. Using the NF1-HGG17 cell line, derived from sporadic gliomas in NPcis mice (Nf1/Tp53 mutant), we performed orthotopic allografting into the striatum of male B6 mice. Single-nucleus RNA sequencing (snRNA-seq) was employed to characterize the cellular composition of the tumor at 28 days post-injection.

overall_design: Orthotopic allografting of 10,000 NF1-HGG17 glioma cells into the striatum of male mice (Nf1+/- or wild-type B6). Tumors were harvested 28 days post-injection for nuclei isolation and single-nucleus RNA sequencing (10X Genomics 3' v3.1).

first: Stephanie

last: Brosius

first: Jonathan

last: Sussman

first: Seka

last: Isabelle

first: Steven

last: Foltz

first: Katherine

last: Labella

first: Isabella

last: DiStefano

first: Kai

last: Tan


title: Ammonia-Induced Dispersion and Proliferation of Actinobacillus pleuropneumoniae Biofilms

city: Wuhan

first: Qiuhong

address: No. 1, Shizishan Street

institute: Huazhong Agricultural University

summary: To elucidate the mechanisms by which ammonia induced the dispersion and proliferation of A. pleuropneumoniae biofilms, NH3·H2O was added to biofilms and planktonic bacteria cultured to the log-phase for short-term stimulation and incubation. Subsequently, planktonic bacteria after ammonia stimulation (PK_NH3, the rapidly proliferating planktonic bacteria after ammonia stimulation), bacteria in the biofilm adhered layer (BF_NH3, adhered biofilm) and the supernatant layer (Up_NH3, bacteria dispersed from the BF layer ) were collected, along with the supernatant layer (Up_DspB) and adhered layer (BF_DspB) treated with DspB, and untreated control groups (PK_Con, Up_Con, BF_Con). RNA was extracted for transcriptome sequencing analysis.

sample_organism: Actinobacillus pleuropneumoniae serovar 1 str. 4074

overall_design: The planktonic cells (PK) of A. pleuropneumoniae 4074, cultured overnight, were inoculated into fresh medium and grown to early-log phase (2 h). Subsequently, 10 mmol/L NH3·H2O was added to the planktonic cells, and the mixture was incubated at 37°C for 2 h. The biofilm-forming cells (BF) of A. pleuropneumoniae were cultured to mid-log phase (5 h) in 12-wells flat bottom cell culture plates. Then, 10 mmol/L NH3·H2O and 2 mg/mL DspB were added separately, and the cultures were incubated at 37°C for 2.5 h. The planktonic and biofilm-associated bacteria were separated.

first: Lu


title: Intrinsically disordered regions restrain genomic targeting of RNA and histone demethylases in mammals and plants

city: Chicago

first: Long

last: Zhao

state: Il

address: 929 E 57th Street

department: Department of Chemistry

institute: University of Chicago

type: Methylation profiling by high throughput sequencing

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

sample_organism:
Arabidopsis thaliana
Mus musculus

platform_organism:
Arabidopsis thaliana
Mus musculus

overall_design: Refer to individual Series


title: A Ketogenic Diet Sensitizes Pancreatic Cancer to Glutamine Metabolism Inhibitors

status: Public on Feb 27 2026

city: Cleveland

first: Omid

last: Hajihassani

state: OH

address: 2103 cornell rd, Wolstein lab 2401

institute: Case Western Reserve Unvieersity

summary: Pancreatic cancer is the third leading cause of cancer-related death in the United States. Current chemotherapy options provide limited benefits. Emerging evidence suggests that a ketogenic diet (KD) exerts anti-tumor effects by reprogramming tumor metabolism and revealing therapeutic vulnerabilities1. Efforts to target glutamine metabolism—an essential pathway in many cancers—have shown promise in preclinical models, clinical efficacy has remained limited. Here, we show that a KD increases tricarboxylic acid (TCA) cycle activity and elevates reliance on glutamine-related metabolites in murine pancreatic cancer models and in vitro under KD-mimicking conditions. This metabolic adaptation occurs in response to reduced glucose availability. We demonstrate that combining glutamine metabolism inhibitors, such as CB839 or 6-diazo-5-oxo-L-norleucine (DON), with a KD leads to robust anti-tumor effects in preclinical models of pancreatic cancer. Thus, metabolic vulnerability induced by dietary intervention provides a rationale for combining glutamine-targeted therapies with a ketogenic diet in future clinical studies.

overall_design: The goal of this experiment was to determine the difference in gene expression of MIA-PaCa2 tumors of mice on a control diet versus the mice on a ketogenic diet

first: Hajihassani

last: Omid


title: The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer

city: Manchester

first: Martin

middle: James

last: Baker

state: England

address: 555 Wilmslow Rd

department: Division of Cancer Sciences

institute: University of Manchester

summary: The E3 ubiquitin ligase HUWE1 modifies a diverse network of substrate proteins by ubiquitination, through which it regulates various intracellular processes and contributes to both oncogenic and tumour suppressor mechanisms in different cancer contexts. Here, by analysing human lung adenocarcinoma (LUAD) patient samples, we reveal that HUWE1 protein expression is commonly upregulated in LUAD tumours compared to normal adjacent lung tissue and that this increase is associated with tumour stage. Using multiple, independent murine models of LUAD initiation and growth, we identify that Huwe1 is essential for mutant Kras-induced lung tumour development and reveal a novel, p53-independent requirement for Huwe1 in LUAD. Mechanistically, we demonstrate induction of senescence following HUWE1 depletion - characterised by impaired proliferation, an atypical cell cycle distribution, emergence of morphologically abnormal enlarged cells, increased β-galactosidase activity, and transcriptional reprogramming associated with inflammatory senescence-associated secretory phenotype (SASP) signalling and NFκB activation. Together, these data highlight a crucial role for HUWE1 in mutant Kras-induced LUAD tumorigenesis and in the continued growth and proliferation of established LUAD cells, confirming HUWE1 as a rational therapeutic target for LUAD.

overall_design: Transcriptomic analysis of H358 LUAD cells -/+ treatment with doxycycline to induce expression of control (shCTRL) or HUWE1 targeting (shHUWE1) shRNA constructs. Three biological replicates of each condition.

first: Joshua

last: Searle

first: Matteo

last: Menotti

first: Anshuman

last: Chaturvedi

first: Mathew

last: Carter

first: Fiona

last: Blackhall

first: Angeliki

last: Malliri

first: Colin

last: Lindsay


title: Hdac11 promotes idiopathic pulmonary fibrosis through macrophage M2-type polarization and myofibroblast differentiation by inhibiting Parkin-dependent mitophagy

city: Wuxi

first: yunjuan

last: Nie

state: Jiangsu

address: 1800 Lihu Avenue

department: Wuxi School of Medicine

institute: Jiangnan University

summary: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which macrophages play a central role in driving fibrogenesis. In this study, we observed marked upregulation of histone deacetylase 11 (Hdac11) in lung tissues from IPF patients, lung organoid models, and bleomycin‑induced fibrotic mouse lungs, with predominant expression in alveolar macrophages. Genetic deletion of Hdac11 or adoptive transfer of Hdac11‑deficient macrophages significantly reduced fibrotic progression. Hdac11 loss impaired M2 macrophage polarization and macrophage‑to‑myofibroblast transition, leading to decreased myofibroblast accumulation and reduced profibrotic gene expression. Mechanistically, Hdac11 directly deacetylates Parkin at lysine 76, promoting its ubiquitination and proteasomal degradation, thereby suppressing Parkin‑mediated mitophagy. Impaired mitophagy resulted in mitochondrial dysfunction that enhanced profibrotic macrophage activation. Pharmacological inhibition of Hdac11 alleviated bleomycin‑induced lung fibrosis. These findings identify Hdac11 as a regulator of Parkin‑dependent mitophagy in macrophages and suggest Hdac11 inhibition as a potential therapeutic strategy for IPF.

overall_design: Alveolar macrophages (AMs) from C57BL/6 mice were stimulated with IL‑33 (10 ng/mL) at 0, 3, 6, 12, 24, 48, 72, and 96 h — with three biological replicates at 0 and 24 h and one replicate at each other time point. In parallel, lung-derived primary fibroblasts were treated with TGF‑β1 (10 ng/mL) for 24 h. Transcriptomic profiles for all samples were generated via Illumina RNA‑seq.

first: Yunjuan

first: Li

last: Xu

first: Yanyan

last: Liu

first: Jiao

last: Li

first: Manjula

last: Karpurapu

first: Huaqi

last: Guo

first: Gaoshang

last: Chai


title: Epigenetic Memory of Intestinal Epithelial Cells in Inflammatory Bowel Disease [ATAC-seq]

city: Rochester

first: Aditya

last: Bhagwate

state: MN

address: 200 1st Street SW

institute: Mayo Clinic

summary: The pathogenesis of Inflammatory Bowel Disease (IBD) is a multifactorial process characterized by inflammation and damage to the intestinal barrier, which is made up of intestinal epithelial cells (IECs). Since IBD is a remitting and relapsing disease, we postulated that epigenetic memory exists in IECs following an inflammatory encounter. The objective of this study was to uncover the mechanisms of a retained altered IEC epigenetic landscape in the context of IBD. We have generated adult stem cell organoids (containing all epithelial cell lineages) from patients with Ulcerative Colitis (UC); two organoid lines per patient were propagated: 1) from a site of active inflammation and from the same patient, and 2) a never inflamed region. We performed Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and bulk RNA-seq on each organoid line. Established bioinformatic pipelines were used to determine significantly different chromatin accessibility and differentially expressed genes. Functional significance of the open chromatin regions was assessed by pathway and motif analysis. Treatment with TNF-alpha (10 and 100ng/ml) for 24 hours on the organoids was performed to determine re-activation of pro-inflammatory genes. This study shows for the first time that epithelial cells derived from organoids of IBD patients retain an epigenetic memory of the prior inflammatory state.

overall_design: Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and bulk RNA-seq on organoids

first: Brooke

middle: R

last: Druliner

first: Feda

last: Hamdan


title: STARR-seq from A549 (ENCSR005XEA)

city: Stanford

first: ENCODE

last: DCC

address: 300 Pasteur Dr

institute: ENCODE DCC

summary: For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: A pig model of human radiation-induced veno-occlusive liver disease reveals ferroptosis as a therapeutic target

city: Shanghai

first: Lijian

last: Hui

address: yueyang road 320

department: SIBCB

institute: CEMCS, CAS

summary: Radiation-induced liver disease (RILD) is a significant complication of radiotherapy and radiation-based preconditioning for cell transplantation. Despite its importance, understanding its pathogenesis and developing effective therapies have been challenging due to the lack of an appropriate animal model that faithfully reproduces the pathological hallmarks of RILD. In this study, given their anatomical and physiological similarities to humans, we used Bama miniature pigs to establish a reliable large-animal model of RILD through a dose-escalation study using hypofractionated stereotactic body radiation therapy. Pigs receiving 40 Gy radiation developed RILD symptoms and exhibited significant liver dysfunction within 4 weeks, closely resembling human disease progression. Moreover, the pigs developed key pathological RILD hallmarks, including hepatic veno-occlusive disease, centrilobular necrosis, liver fibrosis, and compromised liver regeneration. Through single-nucleus RNA sequencing (snRNA-seq) and histological analyses, we found that hepatocytes in the RILD pig model underwent ferroptosis. Notably, treating these pigs with the ferroptosis inhibitor Liproxstatin-1 after irradiation significantly reversed the symptoms and pathological features of RILD and enhanced liver regeneration, particularly by promoting the proliferation of hepatocytes and endothelial cells. These results underscore the role of hepatocyte ferroptosis as a pivotal driver of RILD and highlight its potential as a therapeutic target. Our study provides a valuable large-animal platform for advancing the understanding and treatment of RILD, as well as optimizing radiation-based therapies and preconditioning strategies.

overall_design: To comprehensively understand the pathogenesis and molecular mechanisms underlying RILD in the early stages, we performed snRNA-seq on liver biopsy samples from the 40 Gy group on day 14 and non-irradiated controls (0 Gy).  To further investigate the therapeutic mechanism of Lip-1 in preventing RILD, we performed snRNA-seq analysis on liver biopsy samples from pigs in the control group (40 Gy) and Lip-1 treatment group (Lip-1) 14 days post-irradiation.

first: Zhen

last: Sun

first: Ludi

last: Zhang

first: Baihua

last: Wu

first: Chandan

last: Guha


title: Multi-omic characterization of a soil microbial consortium reveals critical role of succinate and glutamate metabolism during calcium carbonate precipitation

status: Public on Feb 26 2026

city: Richland

first: Ryan

last: McClure

state: Washington

address: 11829272 Battelle for the US DOE, 790 6th Street

department: Microbiology

institute: Pacific Northwest National Laboratory

summary: Microbially induced calcium carbonate precipitation (MICP) holds potential for soil stabilization and carbon sequestration efforts. While the biogeochemical pathways and enzymes driving MICP are known, the microbial metabolic networks and community dynamics underlying such processes remain poorly characterized. To address this gap, we interrogated a MICP-capable four-member consortium of soil bacteria termed carbon storing consortium - A (CSC-A). Prior work shows that CSC-A yields carbonate at a higher quantity compared to the sum of carbonate individually produced by each member, suggesting MICP is driven by consortium dynamics.Thus, we applied a multi-omic integration approach of genomics, transcriptomics, and metabolomics to investigate potential inter-species interactions that may influence the MICP phenotype. Genomic life history characterizations identified evidence of specialization by two members, while metatranscriptomic perturbation suggested that R. qingshengii is a keystone species when grown in urea, a key molecule to the MICP process. By comparing individual species’ metabolomes to the metabolic profile of a shared well, we identified over 200 metabolites predicted to be produced or consumed by CSC-A. Integrating both data types and mapping them to the KEGG reactome highlighted over 20 different enriched pathways with reactions related to glutamate metabolism, succinate metabolism, and branched chain amino acid biosynthesis. As succinate metabolism was a major node in this network we applied laboratory assays to confirm that succinate led to increased carbonate precipitation by CSC-A, a critical validation of our modeling approach. By isolating and identifying the interconnected metabolic components underlying MICP in CSC-A, we identified keystone taxa, metabolites, and pathways important for future optimization of the application of this consortium to carbonate precipitation.

sample_organism:
Curtobacterium flaccumfaciens
Microbacterium foliorum
Bacillus toyonensis
Rhodococcus qingshengii

overall_design: RNA-seq profiling of CSC-A as well as CSC-A lacking   C. flaccumfaciens in the presence and absence of urea-enriched media, with samples taken at time points of 0 hours, 24 hours, and 48 hours and CSC-A lacking R. qingshengii in urea enriched media with samples taken at time points of 24 hours and 48 hours.

first: Lin

last: Tesia T.

first: Anthony

last: Winston

first: McClure

last: Ryan

first: Mitchell

last: Hugh


title: NKG2A inhibition promotes NK cell-CD8+ T cell interactions in support of improved anticancer immunity in ovarian carcinoma

city: Prague

first: Michal

last: Hensler

state: Prague 7

address: Jankovcova 1518/2

country: Czech Republic

institute: Sotio Biotech a.s.

summary: Natural killer (NK) cells contribute to tumor immunosurveillance, yet their phenotypic and functional heterogeneity and impact on anti-tumor immunity remain incompletely understood. Here, using an integrated set of transcriptomic, spatial, and functional assays, we demonstrate that advanced non-small cell lung carcinoma (NSCLC), which is generally considered an immunologically “hot” tumor – contains elevated levels of intratumoral cytotoxic NK1 (CD56dim) and NK3 subsets, which exhibit robust clinically relevant effector functions, localze preferentially within tumor cores, and spatially interact with CD8+ T cells in mature tertiary lymphoid structures (mTLSs). In contrast, the NK cell compartment of immunological “cold” tumors such as high-grade serous ovarian carcinoma (HGSOC) – which generally contains immature TLSs and ICI-resistant TCF1-TIM3+CD8+ CTLs – is enriched in functionally exhausted NK2 (CD56bright) NK cells expressing high levels of TIM3 and NKG2A. Functional studies in HGSOC patient samples and syngeneic mouse models reveal that bidirectional crosstalk between NK cells and CD8⁺ T cells is essential for anti-tumor immunity, and that disrupting this interaction—via CD8⁺ T cell or NK cell depletion—promotes NK cell exhaustion and CD8⁺ T cell dysfunction. Importantly, blockade of NKG2A restores NK cytotoxicity and promotes CD8⁺ T cell effector responses, and when combined with PD1 inhibition, significantly enhances survival in murine HGSOC models. Our findings highlight the NKG2A–HLA-E axis as a clinically actionable checkpoint in tumors with impaired NK cell–mediated immunity, and delineate the spatial and functional interplay between NK cells and CD8⁺ T cells as a determinant of anti-tumor immune efficacy.

overall_design: A total of 4 samples were analyzed, including 2 HGSOC and 2 NSCLC samples.

first: Teraza

last: Lanickova

first: Artemis

last: Angelidou

first: Veronika

last: Niederlova

first: Jitka

last: Fucikova


title: Enhanced mitophagy promotes lung repair and regeneration by restoring epithelial metabolic fitness [RNA-Seq]

first: pei

last: wu

address: 393 Middle Huaxia Road

institute: ShanghaiTech University

summary: Alveolar Type II cells (AT2s) are the stem cells in the alveoli, responsible for both alveolar homeostasis and regeneration. Mitochondrial dysfunction has been reported in the AT2 cells from both chronic and acute injury induced alveolar diseases, including idiopathic pulmonary fibrosis (IPF) and viral pneumonia. Here, we demonstrate that genetic depletion of Ubiquitin Specific Peptidase 30 (USP30), a negative regulator of mitophagy, boosts mitophagy and restores mitochondrial function, leading to protection from injury induced AT2 apoptosis and increased AT2 stem cell activity. Both global Usp30 knockout (KO) and AT2-specific Usp30 KO protects the mice from bleomycin induced lung fibrosis and influenza puneumonia. Moreover, pharmaceutical inhibition of USP30 using a small molecule inhibitor effectively alleviates lung fibrosis and influenza pneumonia. Our study underscores a therapeutic potiential of USP30 inhibition for the treatment of injury induced alveolar diseases, offering a promising strategy for treating injury induced diseases

overall_design: RFP+ AT2 cells were flow-sorted from tamoxifen-treated WT-sftpc-creert2 and Usp30-Sftpc-creert2 mice at day 14 after saline or bleomycin treatment

first: Ying

last: Xi

first: Pei

first: Jiawei

last: Chen


title: ZNF200 RNA-seq in H1299 cell line

city: hefei

first: xiaozheng

last: wei

address: tanghelu

institute: Anhui Medical University

summary: We aimed to detect the mRNA expression levels in stable-transfected H1299 cells after transfection with ZNF200 knockdown or control virus.

overall_design: Extract total RNA from H1299 cell line after transfection with ZNF200 knockdown or control virus, each sample use one well in 6 wells plate H1299 cells.

first: Weixiao

last: Zheng

first: Qian

last: Dai

first: Yanke


title: ZNF200 interacts with DDX17 to regulate the transcriptional activity of RBP-J. [ChIP-Seq]

summary: In order to explore the molecular mechanism of ZNF200 in the development of NSCLC, we conducted CUT&Tag experiments in the H1299 cell line using IgG and ZNF200 antibodies. Based on previous exploratory experiments, we found an interaction between DDX17 and ZNF200. Therefore, we stably transfected DDX17-HA into H1299 cells and performed CUT&Tag experiments using IgG and ZNF200 antibodies. We then discovered that both ZNF200 and DDX17 act on the promoter region of RBP-J. Consequently, in the DDX17-HA stable transfectants of H1299,H520 and A549 cells, we knocked down ZNF200 and performed CUT&Tag experiments using HA antibodies. At the same time, we knocked down ZNF200 and DDX17 in the H520and A549 cell lines, respectively. Since H3K4me3, as an epigenetic modification, is a hallmark of the active status of gene promoter regions and is usually associated with the activation of gene expression, we subsequently used antibodies against histone H3K4me3 for the CUT&Tag experiments.

overall_design: CUT&Tag of IgG and ZNF200 in H1299 cells, CUT&Tag of IgG and ZNF200 after stable transfection of DDX17-HA in H1299 cells, and after knocking down ZNF200 in H1299,H520 and A549 cells stably transfected with DDX17-HA, as well as CUT&Tag of HA, and also knocking down ZNF200 and DDX17 in H520 and A549 cell lines compared to the control group for H3K4me3 CUT&Tag.

last: Zhang


title: Enhanced mitophagy promotes lung repair and regeneration by restoring epithelial metabolic fitness [AT2s RNA-Seq]

overall_design: RFP+ AT2 cells were flow-sorted from tamoxifen-treated WT-sftpc-creert2  and Usp30-Sftpc-creert2 mice at day 14 after influenza infection

last: Wu


title: TopBP1 controls conventional dendritic cell development and Flt3L-driven cDC1 differentiation via PU.1 and IRF8

city: Suwon-si

first: Minsuk

last: Cha

address: 2066, Seobu-ro, Jangan-gu

country: South Korea

institute: Sungkyunkwan University

summary: DNA topoisomerase II-binding protein 1 (TopBP1) plays a vital role in V(D)J recombination during B and T cell development. However, its role in the development of conventional dendritic cells (cDCs) remains unexplored. Mice with DC-specific depletion of TopBP1 (TopBP1cKO) showed accelerated tumor progression due to impaired anti-tumor immunity, characterized by cDC deficiency and pre-DC accumulation. Notably, Flt3 ligand (Flt3L)-mediated tumor immunotherapy was ineffective in TopBP1cKO tumor-bearing mice. Our study demonstrates that TopBP1 is required not only for the steady-state differentiation of total cDCs, including both cDC1 and cDC2, but also for the terminal differentiation of XCR1⁻CD24⁺ emergency progenitors (EPs; CD11c⁺cKit⁺) into XCR1⁺CD24⁺ cDC1s in response to Flt3L. Furthermore, we revealed that TopBP1 directly interacts with PU.1 and IRF8, key transcription factors (TFs) required for cDC development, triggering the expression of their downstream target genes. These findings identify TopBP1 as a crucial factor for cDC development and Flt3L-driven EP differentiation into cDC1s, revealing that the function of key TFs for cDC development is mediated via interaction with TopBP1. Our work underscores the importance of TopBP1 in promoting cDC development and the therapeutic efficacy of Flt3L-mediated tumor immunotherapy.

overall_design: RNA-seq profiling of CD24⁺ EP(Emergency progenitor; CD11c+CD117+)s from the spleen of TopBP1^fl/fl (littermate) and TopBP1 fl/fl, CD11c-cre (cKO) mice on day 9 after Flt3L-Ig injection

first: Min-Suk

first: Yong-Soo

last: Bae


title: Enhanced mitophagy promotes lung repair and regeneration by restoring epithelial metabolic fitness

overall_design: On day 18, CD45+ and CD45- cells were flow-sorted from bleomycin-treated wild-type (WT) and USP30-/- mice for single-cell RNA sequencing (scRNA-seq) analysis.


title: Genome reorganization and its functional impact during breast cancer progression

status: Public on Feb 25 2026

city: Bethesda

first: Kathleen

middle: Shaindel Metz

last: Reed

state: MD

address: 41 Medlars Dr, B507

department: Genetics and Molecular Biology

institute: National Cancer Institute, NIH

summary:
To explore how chromatin structure and epigenetic parameters of genome architecture changes during cancer progression at a fine scale and genome-wide, we generated high-resolution Micro-C contact maps in non-malignant, pre-cancerous, and metastatic MCF10 breast cancer epithelial cells. We profiled progression-associated reorganization of chromatin compartments, topologically associated domains (TADs), and chromatin loops, and also identified invariable chromatin features. We find large-scale compartmental shifts occur predominantly in early stages of cancer development, with more fine-scale structural changes in TADs and looping accumulating during the later transition to metastasis. We related these structural features to changes in gene expression, histone marks, and potential enhancers and found a large portion of differentially expressed genes physically connected to distal regulatory elements. While changes in chromatin loops were relatively rare during progression, differential loops were enriched for progression-associated genes, including those involved in proliferation, angiogenesis, and differentiation. Changes in either enhancer-promoter contacts or distal enhancer activity were accompanied by differential gene regulation, suggesting that changes in chromatin contacts are not necessary but can be sufficient for gene regulation. Together, our results demonstrate a functionally relevant connection between gene regulation and genome remodeling at many key genes during cancer progression.

This SuperSeries is composed of the SubSeries listed below.

middle: S

last: Metz Reed

first: Tom

last: Misteli

first: Andrew

last: Fritz

first: Haley

last: Greenyer

first: Seth

last: Frietze

first: Janet

last: Stein

first: Gary


title: Time-Course RNA Sequencing of Alveolar Type 2 Cells Following Influenza Infection

first: pei

last: wu

summary: The influenza-infected mouse model serves as an acute lung injury model, leading to extensive collapse of the alveolar regions. In this project, we aimed to investigate the effects of influenza infection on the transcriptome of type II alveolar epithelial cells. We isolated type II alveolar epithelial cells at various time points post-infection for transcriptome sequencing.

overall_design: Alveolar type 2 cells (CD45- EPCAM+ CD31- Integrin β4-) were isolated from the lungs of influenza-infected mice at 0, 2, 6, and 11 days post-infection (dpi) using fluorescence-activated cell sorting (FACS). Subsequently, RNA was extracted from these cells for RNA sequencing.

first: Ying

first: Shenxi

last: Shen


title: The interaction between virus-bound KLF4 and host-bound PARP1 directs the localization of Adeno-Associated Virus Type 2 (wtAAV2) to cellular sites of DNA damage

city: Madison

first: Kinjal

last: Majumder

address: 1525 Linden Drive

department: Oncology

institute: University of Wisconsin

summary: Using a modified iteration of a circular chromosome conformation capture to map the location of viral genomes (V3Cseq), we show that the Adeno-Associated Virus genome localizes spatially with cellular sites of DNA damage during treatment with DDR inhibitors or in the presence of a mutated  KLF4 binding site within the wtAAV2 genome.

overall_design: Identification of the cellular interaction site of Adeno-Associated Virus, and the localization of the resultant DNA damage response. Independent replicates of chromosome conformation capture (designated as V3C in the file name) have been performed. For each time-point or treatment, at least two independent replicates of the indicated assays have been performed.

first: Rhiannon

last: Abrahams

first: Clairine

last: Larsen


title: The nBAF complex subunit CREST/SS18L1 regulates hippocampal memory processes via tyrosine 397 and histone acetyltransferase CBP

status: Public on Feb 24 2026

city: Irvine

first: Kousha

last: Changizi

state: CA

address: 4038 Donald Bren Hall

department: Computer Science

institute: University of California, Irvine

summary: Chromatin modifying/remodeling machinery are important for learning-induced transcriptional activity, yet it remains unclear how they coordinate to drive de novo gene expression for memory formation. Here, we examine the transcription factor known as calcium-responsive transactivator (CREST) in memory formation, synaptic plasticity and learning-induced gene expression. CREST is known to bind major chromatin modifying and remodeling machinery via interaction with CREB-binding protein (CBP) and brahma-related gene 1 (BRG1), respectively. In silico modeling of CREST identified tyrosine 397 (Y397) within the CBP binding domain. Expression of a CREST Y397F point-mutant impairs long-term potentiation and memory. Conversely, expression of a CREST Y397D point-mutant enhances memory in a CBP-dependent manner. Differential gene expression analysis reveals distinct CREST Y397-regulated signatures during memory consolidation. CBP acts through CREB and post-translation modifications to affect memory, but the findings of this study argue for the consideration of the CREST-CBP interaction and Y397 accessibility as factors for memory processes.

overall_design:
To investigate the contribution of CREST to long-term memory formation, we designed condtions for expressing a phospho-null and -mimetic in the adult dorsal hippocampus.
We performed differential gene expression analysis to examine learning-induced gene profiles across 5 distinct conditions consisting of homecage, vehicle and CREST phospho-mutants in 2 different training periods of OLM.

first: Franklin

last: Garcia

first: Maria Farias

last: De Albuquerque

first: Vanessa

last: Johnson

first: Enikö

last: Kramár

last: Changizi Ashtiani

first: Sherif

last: Abdelkarim

first: Agatha

last: Augustynski

first: Dina

middle: P

last: Matheos

first: Joseph

last: Picone

first: Tracy

last: Fetterly

first: Alyssa

last: Rodriguez

first: Jessica

last: Childs

first: Angela

last: Gomez-Arboledas

first: Julia

last: Winter

first: Elizabeth

last: Heller

first: Pierre

last: Baldi

first: Marcelo

last: Wood


title: Genome reorganization and its functional impact during breast cancer progression [RNA-Seq]

first: Kathleen

last: Reed

summary: To explore how chromatin structure and epigenetic parameters of genome architecture changes during cancer progression at a fine scale and genome-wide, we generated high-resolution Micro-C contact maps in non-malignant, pre-cancerous, and metastatic MCF10 breast cancer epithelial cells. We profiled progression-associated reorganization of chromatin compartments, topologically associated domains (TADs), and chromatin loops, and also identified invariable chromatin features. We find large-scale compartmental shifts occur predominantly in early stages of cancer development, with more fine-scale structural changes in TADs and looping accumulating during the later transition to metastasis. We related these structural features to changes in gene expression, histone marks, and potential enhancers and found a large portion of differentially expressed genes physically connected to distal regulatory elements. While changes in chromatin loops were relatively rare during progression, differential loops were enriched for progression-associated genes, including those involved in proliferation, angiogenesis, and differentiation. Changes in either enhancer-promoter contacts or distal enhancer activity were accompanied by differential gene regulation, suggesting that changes in chromatin contacts are not necessary but can be sufficient for gene regulation. Together, our results demonstrate a functionally relevant connection between gene regulation and genome remodeling at many key genes during cancer progression.

overall_design: Paired-end rRNA-depleted RNA-Seq in MCF10A, MCF10AT1, and MCF10CA1a cell lines (3 biological replicates per cell line).

first: Tom

last: Misteli

first: Andrew

last: Fritz

first: Haley

last: Greenyer

first: Seth

last: Frietze

first: Janet

last: Stein

first: Gary


title: Genome-wide transcriptome analysis upon KSHV lytic reactivation

city: Boston

first: Soo Mi

last: Lee

address: 3 BLACKFAN CIRCLE, CLS 417

department: Pathology

institute: BIDMC/Harvard Medical School

summary:
Purpose: To characterize genome-wide mRNA expression profiles in the context of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic reactivation.
Methods: We utilized a well-established model of KSHV reactivation, the doxycycline (Dox)-inducible KSHV producer cell line iSLK.219, which contains a latent KSHV genome and a Dox-inducible KSHV lytic switch protein RTA (replication and transcription activator) to mediate efficient reactivation and entry into the lytic cycle upon Dox treatment. We performed mRNA-sequencing (mRNA-seq) of RNA isolated from latent KSHV-infected iSLK.219 cells at 0 h or lytic iSLK.219 cells at 72 h post Dox-induced KSHV lytic reactivation using Illumina. The mappable reads were aligned to the human genome or the KSHV genome using Bowtie.
Results: We analyzed global transcriptome changes in iSLK.219 cells during the latency to lytic transition and found that reactivated lytic iSLK.219 cells exhibited an increased abundance of cellular genes involved in cell cycle, DNA replication, and nuclear division, consistent with lytic infection activating mitogenic signaling to support viral DNA replication. In addition, expression of key viral lytic genes with strong mitogenic activities, including vIL-6 (K2), K1, and the KSHV-encoded chemokines, vCCL1 (K6), vCCL2 (K4) and vCCL3 (K4.1), were markedly induced during lytic KSHV replication.
Conclusions: These results confirm that the gene expression profile of reactivated lytic iSLK.219 cells exhibit some key hallmark features of KSHV lytic reactivation.

first: SooMi

first: Frank

last: Slack


title: Phosphorylation of SF3B1 by CDK11 1 orchestrates spliceosome activation via SNIP1 dependent RES complex recruitment

city: Pamplona

first: Igor

last: Ruiz de los Mozos

state: Nyp

address: C. del Sadar s/n

department: Department of Personalized Medicine

country: Spain

institute: NASERTIC

summary: Splicing Factor 3b Subunit 1 (SF3B1), a core component of the spliceosome, undergoes dynamic phosphorylation and dephosphorylation during the splicing cycle to regulate pre-mRNA splicing. Twenty-eight threonine/proline repeats are phosphorylated by CDK11 during spliceosome activation and remain phosphorylated in the catalytically active spliceosomes. The function of phosphorylated SF3B1 (P-SF3B1), and the identity of spliceosomes stalled by CDK11 inhibition remain unclear. Using quantitative proteomics of chromatin-associated spliceosomes, we identify a previously uncharacterized intermediate complex BOTS964, arrested by CDK11 inhibitor OTS964, that incorporates the nineteen-related (NTR) but not nineteen (NTC) complex. iCLIP-seq revealed that P-SF3B1 engages with the U6 snRNA internal stem-loop (ISL), suggesting a potential role in stabilizing the RNA catalytic core. We further demonstrate that P-SF3B1 is recognized by forkhead-associated (FHA) domain of SNIP1, which promotes recruitment of retention and splicing (RES) complex during spliceosome activation. Acute SNIP1 depletion disrupts RES incorporation, causes widespread splicing defects, and promotes hyperphosphorylation of SF3B1 by CDK11. Mutations in SNIP1 FHA domain, including the neurodevelopmental disorder associated E366G variant, impair P-SF3B1 binding, pre-mRNA splicing, and cell viability. Together, these findings uncover the phosphorylation-dependent CDK11/P-SF3B1/SNIP1 signaling axis that is critical for pre-mRNA splicing and cellular proliferation and provide a mechanistic insight into its dysregulation in disease.

overall_design: Examination of P-T211-SF3B1 and P-T235-SF3B1 iCLIP in the presence or absence of OTS964 inhibitor on HCT116 cells

first: Pavla

last: Gajduskova

last: Ruiz de Los Mozos

first: Milan

last: Hluchy

first: Antonina

last: Myskova

first: Katerina

last: Zabrady

first: Peter

last: Manik

first: Neda

last: Dragisic

last: Hanakova

first: David

last: Potesil

first: Sara

last: Bologna

first: Jiri

last: Novacek

first: Caroline

middle: C

last: Friedel

first: Konstantinos

last: Tripsianes

first: Zbynek

last: Zdrahal

first: Dalibor

last: Blazek


title: RNA-seq analysis of the human SC1 lymphoma cell line after bryostatin treatment

status: Public on Feb 23 2026

city: San Francisco

first: Huimin

last: Geng

address: 513 Parnassus Ave., MSB HSW 1201

department: Department of Laboratory Medicine

institute: UCSF

summary: RNA-seq analysis was performed on a CD72 antigen-low human lymphoma cell line (SC1) to examine gene expression changes after bryostatin treatment compared to DMSO

overall_design: RNA-seq profiling of total RNA transcript levels in human SC1 lymphoma cell line treated with bryostatin or DMSO (vehicle), with three samples per condition.

first: Adila

last: Izgutdina

first: Arun

last: Wiita