title: Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins [scRNA-seq LCMV]

first: Alina

last: Ulezko Antonova

first: Siling

last: Du

first: Marco

last: Colonna

first: Simone

last: Brioschi


title: GATA4 loss promotes mutant Kras-driven pancreatic ductal adenocarcinoma in the absence of canonical precursor lesions [bulk RNA-Seq]

status: Public on May 12 2026

city: Madrid

first: Jaime

last: Martinez de Villarreal

state: Madrid

address: Melchor Fernández Almagro, 3

department: Molecular Oncology Programme

country: Spain

institute: CNIO

type: Expression profiling by high throughput sequencing

summary: GATA6 and GATA4 play key roles in pancreatic development and are essential to maintain the classical transcriptional program in pancreatic ductal adenocarcinoma (PDAC). Using genetic mouse models we show that, in contrast to GATA6, GATA4 is dispensable for the maintenance of acinar homeostasis in the adult pancreas. Deletion of Gata4 in mice expressing mutant Kras in the embryonic pancreas (KG4C) leads to PDAC development in the absence of acinar-to-ductal metaplasia (ADM), pancreatic intraepithelial neoplasias (PanINs), or other canonical precursor lesions present in Gata4-proficient (KC) mice. Similar observations were made when Gata4 was selectively inactivated in adult, Kras-mutant, acinar cells, We identify Pale Acinar Lesions (PALes) as a previously unrecognized pancreatic lesion, distinct from ADM and PanINs, present in KC and KG4C mice but not in control mice. PALes display weak expression of acinar and ductal markers and lack mucins; they have lower proliferation rates than PanINs. RNA-seq and ChIP-seq reveal that GATA4 and GATA6 partially share genomic binding sites and transcriptomic effects, but they exert opposing influences on mutant Kras–induced, hematopoietic cell–dependent, transcriptional inflammatory signatures. Adenoviral-mediated pancreatic expression of IL17 restored the formation of ductal lesions in KG4C mice but failed to rescue PanIN development. Our data suggest that GATA4 functions through the coordinated action of multiple inflammatory factors that are required for ADM/PanIN formation but are dispensable for PDAC development. Collectively, these findings challenge current paradigms of PDAC initiation and progression.

overall_design: RNA-seq transcriptomic profiling of whole pancreatic tissue obtained from mice with embryonic mutant Kras-G12Vgeo knockin and Gata4 knockout in pancreatic epithelial cells prior to major histological changes (8-10 weeks old animals, no treatment).

first: Madriles

last: Francesc

first: P. de Andrés

last: Mónica

first: Chesnokov

last: Mikhail

first: Martinez de Villarreal

last: Jaime

first: Real

last: Francisco X.


title: Murine Endothelial Chromatin Remodeling Enzymes Modulate Plasmin Activity  and Sterile Inflammation to Prevent Lethal Embryonic Liver Deterioration

city: Oklahoma

first: Courtney

middle: T

last: Griffin

state: OK

address: 825 NE 13th Street

department: Cardiovascular

country: USA

institute: Oklahoma Medical Research Foundation

summary: Transcriptional changes in liver sinusoidal endothelial cells (LSECs) from mutant mouse embryos lacking endothelial chromatin-remodeling enzymes need investigation. In this study, we compared the transcriptomes of CD146+ LSECs and the non-EC liver cells from control, Chd4fl/fl;Brg1fl/+;VE-cadherin-Cre+, Chd4fl/+;Brg1fl/fl;VE-cadherin-Cre+, and Chd4fl/fl;Brg1fl/fl;VE-cadherin-Cre+ mice at embryonic day 12.5. Our results show that inflammation-related gene expression is upregulated in endothelial mutants lacking Chd4 and returns to normal when both Chd4 and Brg1 are deleted.

overall_design: Bulk RNA sequencing was conducted on isolated LSECs and non-EC liver cells from control, Chd4fl/fl;Brg1fl/+;VE-cadherin-Cre+, Chd4fl/+;Brg1fl/fl;VE-cadherin-Cre+, and Chd4fl/fl;Brg1fl/fl;VE-cadherin-Cre+ embryos at E12.5 (n=3 for each genotype). This resulted in 12 samples for LSECs and 12 samples for non-EC liver cells.

first: Meng-Ling

last: Wu


title: Chromatin accessibility differences in RXRαβ-deficient and WT alveolar macrophages using the CD11c-Cre+ mouse model (ATAC-Seq)

status: Public on May 13 2026

first: Mercedes

last: Ricote

address: Darwin 3

institute: CNB-CSIC

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The main objective of this study was to compare the epigenetic landscape of alveolar macrophages in mice lacking both RXR subtypes (RXRα and RXRβ), to identify differences in the chromatin accessibility that are controlled by these nuclear receptors.

overall_design: WT and RXRαβ-deficient alveolar macrophages were obtained by bronchoalveolar lavage (BAL) and sorting as individual biological replicates. Transposition was performed using Tn5 enzyme (Illumina), applying size selection. Sequencing was performed in duplicate using 2×50 HiSeq 3000 (Illumina) and with an average of 25 million paired-end reads per sample.

first: Jesús

last: Porcuna

first: Jorge

last: Mínguez-Martínez


title: Bulk RNA Sequencing of 3 DIPG Cases

status: Public on Dec 22 2025

city: New York

first: Lorenzo

last: Tomassoni

address: 1130 St Nicholas Avenue

institute: Columbia University

summary: Tumors of 3 DIPG Patients have been subjected to Bulk RNA Sequencing as part of a program at Rady Children's Hospital

overall_design: Tissue from 3 untreated DIPG Tumors was isolated and prepared for Bulk RNA-Sequencing

first: Ester

middle: C

last: Fernandez

first: Xu

last: Zhang

first: Junqiang

last: Wang

first: Aleksandar

last: Obradovic

first: Pasquale

last: Laise

first: Aaron

first: Lukas

last: Vlahos

first: Hanna

middle: E

last: Minns

first: Diana

middle: V

last: Morales

first: Christian

last: Simmons

first: Matthew

last: Gallitto

first: Hong-Jian

last: Wei

first: Timothy

middle: J

last: Martins

first: Pamela

middle: S

last: Becker

first: John

middle: R

last: Crawford

first: Theophilos

last: Tzaridis

first: Robert

last: Wechsler-Reya

first: James

last: Garvin

first: Robyn

middle: D

last: Gartrell

first: Luca

last: Szalontay

first: Stergios

last: Zacharoulis

first: Cheng-Chia

first: Zhiguo

first: Andrea

last: Califano

first: Jovana

last: Pavisic


title: Elucidating and Pharmacologic Targeting of Coexisting Diffuse Midline Subpopulation Dependencies

first: Lorenzo

last: Tomassoni

summary: Diffuse Midline Glioma (DMG) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, their treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potential orthogonal drug sensitivities. To address it, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic dependencies of seven coexisting subpopulations identified from tumor biopsies. We then leveraged perturbational profiles of 372 clinically relevant drugs to identify those capable of inverting the activity of subpopulation specific MRs and validated their specificity in vivo. While individual drugs predicted by the analysis to target individual subpopulations—such as avapritinib, larotrectinib, and ruxolitinib—produced only modest tumor growth reduction in orthotopic allograft models, they systemic co-administration induced highly significant survival extension.

overall_design: Single cells were isolated and sequenced from NOD.Cg Prkdcscid/J (NSG) subcutaneously injected with 500,000 patient-derived DMG cells (SU-DIPG-XVII) at five days following treatment with Etoposide, Dinaciclib, Avapritnib, Trametinib, Mocetinostat, Larotrectinib, Ruxolitnib, Napabucasin and Venetoclax

first: Ester

last: Fernandez

first: Xu

last: Zhang

first: Junqiang

last: Wang

first: Aleksandar

last: Obradovic

first: Pasquale

last: Laise

first: Aaron

last: Griffin

first: Lukas

last: Vlahos

first: Hanna

first: Diana

last: Wu


title: Generation of Syngeneic Orthotopic DMG Murine Models

summary: Diffuse Midline Glioma (DMG) syngeneic orthotopic murine mouse models were used as high fidelity model of human DMG tumors as they recapitulate the heterogeneity, cell states and OncoTarget/OncoTreat drug predictions of human DMG tumors.

overall_design: Single-cells were isolated and sequenced from B6(Cg)-Tyrc-2J/J (B6) mice. An intracranial injection with 100,000 DIPG4423 cells was performed and tumor was isolated 3 weeks post-injection for single cell. Additionally, single cells were also isolated from normal brainstem (no tumor) of the same model

last: Minns

last: Morales

first: Christian

last: Simmons

first: Matthew

last: Galitto

first: Hong-Jian

last: Wei

first: Timothy

last: Martins

first: Pamela

last: Becker

first: John

last: Crawford

first: Theophilos

last: Tzaridis

first: Robert

first: James

first: Robyn


title: Elucidating Cooperative Genetic Events in DCIS Progression in Mutant p53-Driven Breast Cancer [WGS]

status: Public on Dec 19 2025

city: Houston

first: Xiaoping

last: Su

state: Texas

address: 7300 Brompton St, Apt 5633

institute: MD Anderson Cancer Center

type: Genome variation profiling by high throughput sequencing

summary: Ductal carcinoma in situ (DCIS) is a mammary lesion characterized by abnormal epithelial cells occurring in mammary ducts while still being confined to the luminal space. Not all DCIS becomes invasive, and no strategy currently exists in patients to stratify indolent DCIS from DCIS at risk of progression. The standard of care includes surgical resection and radiation therapy, which constitutes overtreatment for most women whose DCIS would not progress forward. Several studies of human DCIS and breast cancer suggest that TP53 mutations occur early in DCIS, suggesting a critical role for mutant TP53 in driving disease progression. Using a somatic mouse model of Trp53R245W induced breast cancer (equivalent to the TP53R248W hotspot mutation in humans), we identified DCIS lesions. Through exome-sequencing and low-pass whole genome sequencing, we identified genomic changes shared between DCIS and invasive tumors. This comparison nominated seven murine candidate genes, with eight human orthologs. We assessed the cooperativity of these genes with mutant TP53 in MCF-10A cells using acinar morphogenesis and migration assays. Overexpression of TMEM267 in cells with mutant TP53 caused a significant increase in the filled duct, DCIS-like phenotype. We nominate TMEM267 as a cooperating event with mutant TP53 in DCIS progression.

overall_design: Paired end Low-Pass Whole Genome Sequencing of MaPR245W/+ murine mammary tumors and DCIS lesions

first: Rhiannon

last: Morrissey

first: Guillermina

last: Lozano


title: CAR-neutrophils produced in vivo to treat glioma

status: Public on Jan 04 2026

city: West Lafayette

last: Bao

state: IN

address: 480 Stadium Mall Drive

department: Davidson School of Chemical Engineering

institute: Purdue University

summary: We used single-cell sequencing to compare gene expression and cell subset distribution of in vivo engineered CLTX- CAR- Neutrophils and conventional neutrophils in the tumors.

overall_design: Transcriptome profiles of Conventional neutrophil treated GBM mouse tumor tissue and In vivo Engineered CAR-neutrophil treated GBM mouse tumor tissue were generated by scRNA-seq technology using IIIumina NovaSeq6000

first: Chang

last: Yun


title: Generation of Drug Perturbational Profiles in SF8628 and DIPG6 DMG Cell Lines

first: Lorenzo

last: Tomassoni

summary: 372 clinically relevant drugs, including FDA-approved and late-stage experimental oncology drugs were tested in both SF8628 and DIPG6 DMG Cell Lines

overall_design: RNA-seq profiles were then generated at 24 hours following treatment of each cell line with the 372 drugs—titrated at the lowest of their highest sublethal concentration (48h EC20) or max tolerated serum concentration from the literature—as well as DMSO as vehicle control, using the PLATE-Seq microfluidic automation platform

first: Ester

last: Fernandez

first: Xu

last: Zhang

first: Junqiang

last: Wang

first: Aleksandar

last: Obradovic

first: Pasquale

last: Laise

first: Aaron

last: Griffin

first: Lukas

last: Gallitto

last: Wechsler-Reya

last: Garvin

last: Gartrell

first: Luca

last: Szalontay

first: Stergios

last: Zacharoulis

first: Cheng-Chia

first: Zhiguo

first: Andrea

last: Califano

first: Jovana

last: Pavisic


title: Elucidating Cooperative Genetic Events in DCIS Progression in Mutant p53-Driven Breast Cancer [WES]

first: Xiaoping

last: Su

overall_design: Paired end Whole Exome Sequencing of MaPR245W/+ murine mammary tumors and DCIS lesions

first: Rhiannon

last: Morrissey

last: Lozano


title: Multi-omics analysis identifies intrinsic Trp53 driven metastatic breast cancer subtypes [WES]

summary: Metastatic breast cancer is the leading cause of death amongst patients that develop breast cancer. The molecular drivers of metastatic breast cancer are largely unknown. Treatment of metastatic breast cancer is limited to systemic cytotoxic chemotherapies, which often deteriorate patient quality of life, and tumors often become refractory, resulting in incurable disease. The most frequently mutated gene associated with metastatic breast cancer is TP53. The TP53R248W hotspot missense mutation is associated with poor prognosis in breast cancer. To understand the intrinsic transcriptomic and genomic landscape of metastatic breast cancer driven by mutant p53, we generated a somatic mouse model driven by mammary epithelial specific expression of Trp53R248W. Primary tumors were highly metastatic and reflected the human molecular subtypes of luminal A, luminal B, HER2, and TNBC, with TNBC comprising the majority (79%) of these tumors. Transcriptomic profiling revealed primary tumor heterogeneity characterized by three intrinsic subtypes (1) stem-cell like; (2) well-differentiated metabolic like; and (3) immune suppressed. Stem-cell like tumors activate ribosome biosynthesis and E2F signaling. These tumors harbor amplifications in Met, Birc3, Yap1 and deletions in Nf1, Pik3r1, and Rad17. Well-differentiated metabolic like mammary tumors activate cytochrome P450 enzymes, estrogen signaling and branched chain amino acid degradation and harbor mutations in the Pten pathway. Immune suppressed tumors enrich for processes related to immune suppression. These tumors have high mutation burden, frequently mutate Traf7 and delete Cdkn2a. This is the most comprehensive transcriptomic and genomic profiling of mutant p53 driven breast tumors and sheds light on their heterogenous nature and distinct intrinsic programs that may inform targeted therapy for metastatic breast cancer.

overall_design: Paired end Whole Exome Sequencing of MaPR245W/+ murine mammary tumors collected at end point

first: Joy

last: McDaniel

first: Guillermina


title: Human myeloid ontogeny drives differentiation potential in the brain environment.

status: Public on Feb 26 2026

city: Austin

first: Anna

last: Warden

state: TX

address: 2500 Speedway

institute: University of Texas at Austin

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Overcoming ADC resistance in advanced colorectal cancer by dual targeting of TROP2 and PERK to suppress Wnt/β-catenin signaling

status: Public on Dec 18 2025

city: Ganzhou

first: zhou

last: dongdong

address: hexie avenue

country: China

institute: Gannan Medical University

summary: Targeted therapy for advanced colorectal cancer (CRC) remains a significant clinical challenge. In this study, we systematically examined the anti-tumor efficacy and underlying mechanisms of IMMU132, an FDA-approved anti-TROP2 antibody conjugate linked to the topoisomerase I inhibitor SN-38, both as a standalone treatment and in combination with the PERK inhibitor GSK2606414 in TROP2-positive advanced CRC. We first established that TROP2 expression was markedly elevated in CRC cohorts and correlated with poor patient prognosis. In vitro experiments demonstrated that IMMU132 inhibited CRC cell proliferation and viability in a dose-dependent manner. In patient-derived xenograft (PDX) models, IMMU132 monotherapy significantly inhibited tumor growth. Mechanistically, transcriptomic analysis indicated that PERK, a key factor in endoplasmic reticulum stress (ERS), may serve as a critical synergistic target for IMMU132’s anti-tumour activity. Subsequent screening of various ERS inhibitors revealed that the specific PERK inhibitor GSK2606414 significantly enhanced the effects of IMMU132. In diverse experimental models, including cell lines, organoids, and PDX models, combination therapy exhibited superior anti-tumor effects compared to monotherapy, highlighting a pronounced synergistic effect. Furthermore, transcriptomic analysis showed that combination therapy notably inhibited the Wnt/β-catenin signaling pathway. Gene set enrichment analysis confirmed significant upregulation of Wnt pathway-related genes, while Western blot analysis showed downregulation of key molecules in the Wnt pathway, including β-catenin, GSK3B, JUN, and WNT2B, following combination therapy. These findings suggest that the synergistic anti-tumour effects of IMMU132 and GSK2606414 may arise from their dual modulation of ERS and Wnt signalling pathways, offering novel insights for targeted therapy in advanced CRC and informing strategies for combining antibody-drug conjugates (ADCs).

overall_design: This study systematically characterized TROP2 expression in colorectal cancer through integrated bioinformatics and tissue microarray analysis, with validation across multiple preclinical models. The TROP2-targeting antibody-drug conjugate IMMU132 demonstrated potent monotherapeutic efficacy across diverse molecular subtypes in cell lines, patient-derived organoids and xenografts. Transcriptomic analysis identified PERK, a key endoplasmic reticulum stress regulator, as crucial to IMMU132's mechanism. The specific PERK inhibitor GSK2606414 significantly enhanced IMMU132's anti-tumor effects through synergistic modulation of both endoplasmic reticulum stress and Wnt/β-catenin signaling pathways. These findings elucidate IMMU132's mechanism of action and propose a novel combination strategy with strong translational potential for advanced colorectal cancer therapy.

first: Jie

last: Liu

first: Mei

last: Li

first: Jianming

last: Huang


title: Advancing Lung Tissue Engineering Through the Discovery of Factors that Control Alveolar Epithelial Cell Fate (snRNA-seq from recellularized scaffolds)

city: Durham

first: Laila

last: Roudsari

state: NC

address: 2 Maughan Drive

institute: United Therapeutics

summary: The objective of this study was to evaluate primary, human AT2 cells following seeding into decellularized lung scaffolds.

overall_design: Alveolar type 2 cells were isolated from human lung tissue, expanded in large-scale, and seeded onto decellularized porcine lung scaffolds. Cell culture media was used to promote AT1 differentiation, and samples were taken down over a time-course study. SnRNA-seq analysis was performed on the recellularized lung tissue.

first: Lauren

middle: K

last: Rochelle

first: Rachael

last: Van

first: Richard

last: Ottman

first: Daren

middle: F

last: Robinson

first: Ashley

last: Dockham

first: Amy

last: Smith

first: Daniel

middle: P

last: Keeley

first: Darell

middle: W

last: McCoy

first: Tyler

last: Zimmerman

first: Bryan

last: Fioret

first: Ryan

last: Bonvillain

first: Thomas

middle: H

last: Petersen

first: Sarah

last: Hogan


title: Advancing Lung Tissue Engineering Through the Discovery of Factors that Control Alveolar Epithelial Cell Fate (AT2 scRNA-seq)

summary: The objective of this study was to compare uncultured primary human alveolar epithelial type 2 cells (AT2s) isolated from lungs to AT2s that were expanded in large-scale.

overall_design: Alveolar type 2 cells were isolated from human lung tissue and expanded for 3 passages. Isolated cells (uncultured, UC, or isoAT2), passage 0, and passage 2 cells from 3 donors were analyzed using scRNA-seq.


title: Importance of being non-triplet in alternative splicing

status: Public on Dec 16 2025

city: riverside

first: Shameerudeen

last: Athavudeen

address: 900 university ave

department: Biochemistry

institute: UC Riverside

summary: Alternative mRNA splicing can be used by a cell to regulate gene expression and to generate transcriptomic diversity. Most cases of alternative splicing studied to date are triplet in nature, meaning that both isoforms retain the same translational reading frame. Indeed, non-triplet alternative splicing is sometimes considered evidence of splicing errors or splicing noise. Nevertheless, some examples of functionally important non-triplet alternative splicing exist. We set out to determine the global prevalence, regulation, and function of non-triplet alternative splicing in vivo in C. elegans. We performed RNA-Seq on NMD-deficient mutants and bioinformatically categorized the molecular consequences of non-triplet alternative splicing into three categories: NMD-sensitive isoforms, alternative C-terminal length isoforms, and dual-coding isoforms. We identify hundreds of non-triplet alternative splicing events across these three categories. Genetic and molecular analysis reveals cases of developmental regulation, splicing factor autoregulation, cell-specific splicing patterns, and multiple non-triplet alternative splicing events with physiologically important functions. Together these experiments reveal the importance of non-triplet alternative splicing, a large but underappreciated class of alternative splicing events, for regulating gene expression and generating protein-coding diversity

overall_design: L4 staged animals from wild-type and mutant conditions. RNA extracted, and selected for polyA+ mRNA prior to library generation and short-read sequencing.

first: Adam

last: Norris


title: Gut resident T-bet expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape IV

city: San Diego

first: Eduardo

last: Ansaldo

address: 15550 Torrey Pines Rd

department: IMM

institute: Scripps Research

summary: Intestinal immunity provides defense against enteric pathogens, mediates symbiotic relationships with the resident microbiota, and provides tolerance to food antigens, safeguarding critical nutrient absorption and barrier functions of this mucosal tissue. Despite the large abundance of tissue resident activated T cells, how T cell immunity contributes to these various roles remains poorly understood. Here we describe a previously uncharacterized dominant T-bet expressing Tr1 T cell population in the small intestine lamina propria present at homeostasis. Importantly, this IL-10 secreting CD4^+^T-bet^+^ T cell population appears in the small intestine at the time of weaning independently of the resident microbiota, presenting similar accumulation, functional capacity, and TCR repertoire in germ free conditions. Instead, small intestinal T-bet^+^ Tr1 T cells respond to dietary signals driving their accumulation, suppressive program, and clonal selection; and depend on cDC1s, IL-27 signaling, and T-bet, but not IL-12. Altogether, this work uncovers a previously unappreciated dominant player in homeostatic small intestinal immunity with the potential to play critical suppressive roles in oral tolerance to dietary antigens, raising important implications for the understanding of food allergy and celiac disease.

overall_design: SILP CD4^+^ T cells (Live, CD45+CD90.2+, TCRb+, CD4+) from SPF or GF T-bet-ZsGreen mice that received aCD3 or isotype as described in the corresponding methods section were sorted using a Sony MA900 sorter. RNA was extracted using the Qiagen miRNeasy kit, and sequencing library was prepared using Tecan SoLo total RNA kit for mouse according to manufacturer's instructions. Libraries were sequenced as 1 x 150bp reads on a Illumina NextSeq 2000 using the P3 200 cycle kit.\*

first: Eduard

last: Yong

first: Nathan

last: Carrillo

first: Taryn

last: McFadden

first: Mahnoor

last: Abid

first: Dan

last: Corral

first: Claudia

last: Rivera

first: Taylor

last: Farley

first: Nicolas

last: Bouladoux

first: Inta

last: Gribonika

first: Yasmine

last: Belkaid


title: Gut resident T-bet expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape I

overall_design: SILP CD4 T cells (Live, CD45+CD90.2+, TCRb+, CD4+) from 4 SPF and 4 GF T-bet-ZsGreen mice (adult , steady state) were sorted from samples labeled with TotalSeqC hashtags antibodies (Biolegend) using a Sony MA900 sorter. Sorted cells were pooled during sorting and 32000 cells per lane (total of 8 lanes) were loaded on a Chromium Single Cell Controller (10X Genomics) to encapsulate the cells into droplets. The gene expression (GEX), hashtag oligonucleotide (HTO) and VDJ (TCR) sequencing libraries were prepared using Chromium Single Cell 5’ v2 reagent kits following the manufacturer’s instructions, and sequenced on an Illumina Nextseq2000 platform (NextSeq 1000/2000 P2 reagents).

first: Daniel


title: Bridging the gap of late-gestation nephrogenesis using a non-human primate model

status: Public on Dec 15 2025

city: Cincinnati

first: Kairavee

last: Thakkar

address: 3333 Burnet Ave

institute: Cincinnati Children's Hospital Medical Center

summary:
Background: Prematurity is associated with low nephron endowment and an increased risk of chronic kidney disease. Human nephrogenesis is complete at 34-36 weeks gestation, with 60% of nephrons forming during the third trimester through lateral branch nephrogenesis (LBN). We hypothesized that a differentiated but dividing population of nephron progenitor cells (NPCs) would contribute to the amplification of nephrons in late gestation.
Results: scRNA-Seq of 64,782 rhesus cells revealed 37 transcriptionally distinct cell populations, including 7,879 rhesus NPCs. Pseudotime analyses identified a late gestation-specific lineage branch of differentiated NPC in rhesus that was not observed in mid-gestation humans. Differential expression analyses identified increased SFRP1, FZD4, and TLE2 and decreased FZD7, SHISA2, SHISA3, and TLE4 within the late-gestation rhesus NPC compared to mid-gestation human NPC and increased SEMA3D within the rhesus UB tip, suggesting a compositional shift in WNT and SEMA signaling components within the naive NPC population during LBN.
Conclusion: The rhesus macaque uniquely enables molecular studies of late-gestation primate nephrogenesis.
Our study suggests the hypothesis that a transitional state of self-renewing NPC supported by compositional shifts in key pathways may underlie the switch from branching phase nephrogenesis to lateral branch nephrogenesis and support ongoing nephron formation in late gestation.

overall_design: Single-cell RNA-sequencing (scRNA-Seq) was performed on cortically-enriched fetal rhesus kidneys (n=9) from late second trimester and third trimester during LBN. This data was integrated with publicly available human scRNA-seq datasets from 8-18 weeks gestation kidneys (n=8) using state-of-the-art bioinformatics pipelines. Differentially expressed genes and ligand-receptor interactions were assessed and validated using RNAScopeTM on human and rhesus archival tissue.

first: Meredith

last: Schuh


title: Efficient transgene-free multiplexed genome editing via viral delivery of an engineered TnpB

status: Public on Jan 15 2026

city: Berkeley

first: Marena

middle: Isabelle

last: Trinidad

state: CA

address: 2151 Berkeley Way

institute: Innovative Genomics Institute

summary: Virus-induced genome editing (VIGE) using compact RNA-guided endonucleases is a transformational new approach in plant biotechnology, enabling tissue-culture-independent and transgene-free genome editing. We recently established a transgene-free VIGE approach for heritable editing at single loci in Arabidopsis by delivering ISYmu1 TnpB (Ymu1) and its guide RNA (gRNA) via Tobacco Rattle Virus (TRV). Here, we greatly improved this system by devising a multiple gRNA expression system and by utilizing an engineered high-activity Ymu1 variant (Ymu1-WFR) to develop an efficient multiplexed genome editing approach.

overall_design: Bulk bacterial RNA sequencing was performed to characterize heterologous RNA expression from a defined plasmid construct in Escherichia coli. Cells were grown under identical conditions and induced with arabinose prior to RNA extraction. Each sample represents total RNA isolated from an induced bacterial culture processed through rRNA depletion and small-RNA-seq library preparation. Sequencing reads were aligned to the Ymu1 locus to assess RNA expression profiles.

first: Honglue

last: Shi

first: Kamakshi

last: Vohra

middle: I


title: Impact of Fc engineering on the transcriptional profile of monocytes and interstitial macrophages in the lungs of Hu-FcgR Tg mice after MA30 infection

first: Michael

middle: S.

last: Diamond

state: MO

address: 425 S. Euclid Ave

department: Immunology and Pathology

institute: Washington University School of Medicine

summary: As the SARS-CoV-2 pandemic progressed, many monoclonal antibodies (mAbs) that neutralized infection against initial strains lost potency against later variants due to accumulation of mutations in the spike protein. Nonetheless, some mAbs, including S309, the parent of the therapeutically used sotrovimab, remained protective in animals against Omicron variants despite reduced neutralizing potential, with Fc-mediated effector functions likely sustaining inhibitory activity. Here, we identify Fc variants of S309 that confer enhanced protection against SARS-CoV-2 infection in a humanized Fcg receptor transgenic (Hu-FcgR Tg) mouse model of infection. Versions of S309 that are afucosylated (AFUC) and contain a G236A (GA) mutation in the Fc region showed increased binding to FcgRs IIA, IIIA, and IIIB and enhanced phagocytic activity in cell culture-based assays. Treatment with S309-GA-AFUC resulted in less viral burden, inflammation, and pulmonary ventilatory dysfunction in the lungs of Hu-FcgR Tg mice challenged with SARS-CoV-2 strains compared to the parental S309 mAb or a variant (S309-GRLR) lacking Fc effector functions. The enhanced protection in the lung conferred by S309-GA-AFUC required trafficking of CCR2-expressing monocytes to reduce SARS-CoV-2 viral burden and lung injury. Flow cytometry and RNA sequencing analyses showed that compared to the parental S309 mAb, S309-GA-AFUC treatment reduced the inflammatory state and induced a reparative transcriptional signature in monocytes and interstitial macrophages. Overall, our findings demonstrate that Fc engineering to increase antibody binding to activating FcgRs can strengthen effector functions, shape myeloid transcriptional profiles, and enhance protection against SARS-CoV-2 infection in vivo.

overall_design: RNA-seq profiling of monocytes and interstitial macrophages in the lungs of Hu-FcgR Tg day 3 following MA30 infection

first: Samantha

last: Mackin

first: Courtney

last: Karl

first: Chieh-Yu

last: Liang

first: Maksim

last: Kleverov

first: Mehak

middle: Z

last: Khan

first: Thendral

last: Selvam

first: Matthias

last: Mack

first: Galit

last: Alter

first: Barbara

last: Guarino

first: Davide

last: Corti

middle: A

last: Schmid


title: Gut resident T-bet expressing Tr1 cells driven by dietary signals dominate the small intestinal immune landscape II

first: Eduardo

last: Ansaldo

overall_design: SILP CD4^+^ T cells (Live, CD45+CD90.2+, TCRb+, CD4+) from SPF or GF T-bet-ZsGreen mice that received aCD3 or isotype as described in the corresponding methods section were sorted from samples labeled with TotalSeqC hashtags antibodies (Biolegend) using a Sony MA900 sorter. Sorted cells were pooled during sorting and 40000 cells per lane (total of 4 lanes) were loaded on a Chromium Single Cell Controller (10X Genomics) to encapsulate the cells into droplets. The gene expression (GEX), hashtag oligonucleotide (HTO) and VDJ (TCR) sequencing libraries were prepared using Chromium Single Cell 5’ v2 reagent kits following the manufacturer’s instructions, and sequenced on an Illumina Nextseq1000 platform (NextSeq 1000/2000 P2 reagents).

first: Eduard

first: Daniel

last: Yong

first: Nathan

last: Carrillo

first: Taryn

last: McFadden

first: Mahnoor

last: Abid

first: Dan

last: Corral

first: Claudia

last: Rivera

first: Taylor

last: Farley

first: Nicolas

last: Bouladoux

first: Inta

last: Gribonika

first: Yasmine

last: Belkaid


title: Somatosensory nerves induce the pathologic response to physis injury

city: Baltimore

first: Aaron

last: James

state: Maryland

address: 720 Rutland Avenue, Ross Bldg., Room 529

department: Pathology

institute: Johns Hopkins University

summary: Somatosensory neurons detect a diverse repertoire of stimuli, including in skeletal tissues, in which sensations of pain, pressure, and position are transmitted. Trauma to the physis often leads to pathologic “bony bar” formation, impeding normal growth of the skeleton. The role of somatosensory nerves in detecting and, in turn, regulating physis injury is unknown. Here, we observed prominent sensory nerve growth within the injured physis in mouse and human tissues corresponding to domains of nerve growth factor (NGF) expression. Two independent methods to inhibit tropomyosin receptor kinase A (TrkA) signaling reduced nerve sprouting and attenuated pathologic bony bar formation, whereas conversely sensory neural conditioned medium–treated organ cultures demonstrated the opposing effects. Somatosensory nerve retrograde tracing and single-cell RNA sequencing (scRNA-seq) identified a sensorineural transcriptome evoked by physis injury in mice. Corresponding scRNA-seq of injured mouse growth plates implicated pleiotrophin (PTN) signaling in pathologic growth plate ossification, a finding confirmed by ex vivo organ culture and in vivo knockout in sensory ganglia. Last, FDA-approved long-acting bupivacaine prevented pathological innervation and ossification of the growth plate after injury. These findings suggest that targeting somatosensory nerves could offer previously unrecognized strategies to treat pain and prevent pathologic ossification to optimize patient outcomes after growth plate injury.

overall_design: The samples comprised two distinct tissue types: Dorsal Root Ganglia (DRGs) and growth plates. The experimental design included two groups: a control group and a treatment group. The control group received intraperitoneal injections of the vehicle (DMSO). The treatment group, designated as the 1NMPP1 group, received intraperitoneal injections of 1NMPP1 (5 mM solution, 17 μg/g body weight) at two time points: 48 hours and 2 hours prior to surgery. Following the procedure, animals in the 1NMPP1 group were maintained on drinking water containing 40 μM 1NMPP1 dissolved in ddH2O with 1% PBS-Tween 20.

first: Zhao

last: Li

first: Xin

last: Xing


title: Spatial transcriptomic profiling of human lung tissue in chronic obstructive pulmonary disease (COPD) [Xenium]

status: Public on Dec 09 2025

city: New Haven

first: Maor

last: Sauler

state: CT

address: 300 Cedar Street

department: Section of Pulmonary, Critical Care, and Sleep Medicine

institute: Yale School of Medicine

summary: To spatially contextualize and extend disease-associated cellular states, we generated Xenium spatial transcriptomics data from FFPE lung tissue of 38 participants spanning the COPD disease spectrum. Four tissue microarrays (TMA1–TMA4) were profiled using a custom 480-gene Xenium panel. These data capture the in situ organization of inflammatory, regenerative, and remodeling cell states and reveal spatially localized niches and patterns of cell–cell communications relevant to COPD pathology. This dataset provides high-resolution spatial context for characterizing microenvironmental structure and cell–cell interactions in COPD lung tissue.

overall_design: FFPE lung tissue from 38 participants across the COPD spectrum was organized into four tissue microarrays (TMA1–TMA4), comprising 99 total cores that sampled parenchymal, airway, and vascular regions. Sections (5 µm) from each TMA were mounted on Xenium slides and processed according to the 10x Genomics FFPE workflow (CG000578, Rev C) using a custom 480-gene probe panel (hLung_480g, design ID EM2BNX, v1.0.0). The workflow included deparaffinization, decrosslinking, RNA release, in situ probe hybridization, signal amplification, and multimodal staining. Each slide was imaged and decoded on the Xenium Analyzer to produce cell-resolved transcript and morphology data.

first: Yuening

last: Zhang

first: Huanhuan

last: Wei

first: Jessica

last: Nouws


title: The antibacterial factor APOL3 couples lysosomal damage to mitochondrial DNA efflux and type I IFN induction

first: Ryan

last: Gaudet

state: NY

institute: Columbia Unversity

summary: Lysosomal damage is an endogenous danger signal to the cell, but its significance for innate immunity and how specific signaling pathways are engaged by this stressor remain unclear. Here, we uncover an immune-inducible pathway that connects lysosomal damage to mitochondrial DNA (mtDNA) efflux and type I IFN production. Lysosomal damage elicits mitochondrial outer membrane permeabilization (MOMP) via BAK/BAX macropores; however, the inner mitochondrial membrane (IMM) prevents wholesale mtDNA release in resting cells. Priming with type II IFN (IFN-γ) induced the antibacterial effector apolipoprotein L-3 (APOL3), which upon transient lysosomal damage, targets mitochondria undergoing MOMP and selectively permeabilizes the IMM to enhance mtDNA release and activate cGAS/STING signaling. Biochemical and cellular reconstitution revealed that analogous to its bactericidal detergent-like mechanism, APOL3 solubilizes cardiolipin to permeabilize the IMM. Our findings illustrate how cells use an antibacterial protein to expedite the breakdown of endosymbiosis and facilitate a heightened response to injury and infection.

overall_design: RNA-seq of HeLa NTC and APOL3-/- cells primed with or without IFN-γ, followed by LLOME or DMSO treatment and 8 h recovery.

first: Dominic

last: Ritacco

first: Hamna

last: Shahnawaz

first: Antonia

last: Oduguwa

first: Jacob

last: Hawk

first: Brianna

last: Vizcaino

first: Donna

last: Farber

middle: G


title: Host sex effect on Brugia pahangi

status: Public on Dec 08 2025

first: Julie

last: Dunning Hotopp

state: MD

address: 670 W Baltimore St

institute: University of Maryland, Baltimore

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

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

first: Christopher

last: Holt

first: Robin

middle: E

last: Bromley

first: Benjamin

middle: C

last: Sparklin

first: John

last: Mattick

first: Jeremy

middle: M

last: Foster

first: Michelle

middle: L

last: Michalski


title: Effect of the deletion of the reported ERH binding site embedded in the DGCR8 N-terminus and/or global ERH knockdown on the expression of mature miRNAs

status: Public on Dec 05 2025

city: Innsbruck

first: Sebastian

last: Herzog

address: Innrain 80-82

department: Institute of Developmental Immunology

country: Austria

institute: Medical University of Innsbruck, Biocenter

type: Non-coding RNA profiling by high throughput sequencing

summary: MicroRNAs are small non-coding RNAs that mediate post-transcriptional silencing of most mammalian genes. They are generated in a multi-step process initiated by the Microprocessor, a protein complex composed of DROSHA and DGCR8. Recent studies have described the phenomenon of “cluster assistance”, in which a prototypic primary miRNA hairpin can license the Microprocessor-mediated processing of a clustered suboptimal hairpin in cis. Mechanistic analyses led to the identification of ERH (enhancer of rudimentary homolog) as a critical factor in this process. Notably, ERH has been demonstrated to associate with the N-terminus of DGCR8, but it has not been demonstrated that this complex is required for cluster assistance.  Here, we have used prime editing to generate alleles that encode a DGCR8 Δ103-126Q mutant that cannot bind ERH anymore. In contrast to global ERH knockdown, disruption of the ERH binding motif in DGCR8 affects processing of only a subset of cluster assistance-unrelated pri-miRNAs. Thus, ERH-mediated cluster assistance is independent of its described association with DGCR8, indicating that ERH confers two distinct roles in primary miRNA biogenesis: One driven by its direct binding to the Microprocessor via DGCR8 and the other as a DGCR8/ERH complex-independent factor in cluster assistance.

overall_design: Wild-type 293T cell clones and clones in which the DGCR8 locus had been modified by prime editing to delete the reported ERH binding site were transiently transfected with vectors encoding non-targeting shRNA 1 or 2 as well as with shRNAs targeting ERH. Transfected cells were sorted on day 5 based on expression of a fluorescent marker and directly subjected to total RNA isolation. Total RNA of the respective cell populations was prepared with Trizol, mixed with defined amounts of spike-in control RNAs and subjected to small RNA library preparation.

first: Simon

last: Aschenwald


title: Effect of SAFB1/SAFB2 knockou or ERH knockout on the miRNA transcriptome of murine Baf3 cells

summary: MicroRNAs are small non-coding RNAs that mediate post-transcriptional silencing of most mammalian genes. They are generated in a multi-step process initiated by the Microprocessor, a protein complex composed of DROSHA and DGCR8. Recent studies have described the phenomenon of “cluster assistance”, in which a prototypic primary miRNA hairpin can license the Microprocessor-mediated processing of a clustered suboptimal hairpin in cis. Mechanistic analyses led to the identification of two critical factors for this process, SAFB2 (scaffold attachment factor B2) and ERH (enhancer of rudimentary homolog), but it remains unclear to which extent these factors contribute to and are required for cluster assistance. Here, we have used a previously established dual fluorescence reporter system (doi: 10.1016/j.molcel.2020.05.011) to generate loss-of-function clones for SAFB2 and its closely related family member SAFB1 as well as for ERH.Our data indicate that loss of SAFB1/2 and of ERH results in overlapping, but not identical defects in primary miRNA biogenesis.

overall_design: Small RNAseq data of Baf3 cell expressing fluorescent reporters for the activity of mutated forms of miR-15a and miR-16 (see doi: 10.1016/j.molcel.2020.05.011 for details) that were transduced with vectors encoding Cas9 and sgRNAs targeting Safb1/2, Erh or murine Rag1 (as a control gene not involved in miRNA biogenesis). The polyclonal population of cells that lost the capability to perform cluster assistance in response to SAFB or ERH gene disruption was identified and sorted out based on the derepression of the dsRed-based miR-15a reporter. Total RNA of the respective cell populations was prepared with Trizol, mixed with defined amounts of spike-in control RNAs and subjected to small RNA library preparation.

first: Aschenwald

last: Simon


title: Scaffolding-dependent CASP1 constrains excessive cell-intrinsic inflammatory signaling in leukemia [MDSL]

first: Kwangmin

last: Choi

state: Ohio

address: 333 Burnet Avenue

department: Experimental Hematology & Cancer Biology

summary: The inflammatory cytokine Interleukin-1b (IL-1b is implicated in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). IL-1b processing is regulated by Caspase-1 (CASP1), a protease that is initially expressed as an inactive zymogen (Pro-CASP1) and can be cleaved into its active form. CASP1 cleaves both pro-IL-1b and Gasdermin-D (GSDMD), which mediates IL-1b secretion and consequently pyroptotic cell death. Despite its known role in inflammation, the contribution of CASP1 to leukemogenesis has not been adequately investigated. To address this, we generated Pro-CASP1 knockout (CASP1KO) MDS/AML cell lines and patient-derived samples. As expected, CASP1KO cells were unable to induce pyroptosis or produce IL-1b. Surprisingly, however, these cells also exhibited impaired leukemic cell expansion, increased myeloid differentiation, and significantly reduced leukemic burden when xenografted into mice. Similarly, Casp1-/- pre-leukemic and AML mouse cells were impaired in their clonogenic potential and leukemia development. Notably, restoring IL-1b expression did not rescue the growth defects, suggesting that IL-1b is not the primary driver of CASP1’s role in MDS/AML. Mutation or inhibition of the CASP1 protease activity did not impact MDS/AML cells, indicating that CASP1’s pro-leukemic function is independent of its proteolytic activity. Transcriptomic and functional analyses of CASP1KO cells revealed excessive NF-kB and inflammatory signaling. Suppression of NF-kB activity restored leukemic cell function and viability, indicating that CASP1 acts as a negative regulator of NF-kB activation. We performed a proximity proteomic and computational prediction analysis and identified RPTOR, a component of the mTORC1 complex, as a key interactor of CASP1. Knockdown of RPTOR in CASP1KO cells reduced excessive NF-kB activity and rescued the leukemic growth defect, suggesting that the CASP1–RPTOR interaction regulates NF-kB signaling in leukemia. To target the scaffolding function of CASP1, we developed a PROTAC degrader (dCASP1-55). dCASP1-55 induced NF-kB activation and reduced the colony-forming potential of MDS/AML cells, supporting its potential as a targeted therapy. CASP1 functions as a critical organizational center regulating NF-kB signaling through mTORC1 in MDS/AML, while IL-1b expression is a secondary contributing event.

overall_design: Bulk RNAseq profiling of WT MDSL or Casp1KO MDSL cells generated by Crispr Cas9 and grown in liquid culture, and validated by PCR and western blot.

first: Emma

last: Uible

first: Kathleen

last: Hueneman

first: Erik

last: Vick

first: William

last: Seibel

first: Kenneth

last: Greis

first: Lynn

last: Lee

first: Timothy

last: Chlon

first: Jorge

last: Henao-Mejia

first: Chandrashekhar

last: Pasare

first: Andrew

last: Volk

first: Daniel

middle: T

last: Starczynowski


title: Hierarchical regulation of cerebellar neurogenesis by Sin3A-mediated gene repression

status: Public on Dec 04 2025

city: Nashville

first: Lei

last: Chen

state: TN

address: 465 21st Ave. South

department: Department of Cell and Developmental Biology

institute: Vanderbilt University

summary: Cerebellar granule cells (GCs) are critical for motor and cognitive functions. Lineage tracing studies have identified a hierarchical developmental progression of GC neurogenesis, transitioning from Sox2+ stem-like quiescent cells to Atoh1+ rapidly proliferating granule cell precursors (GCPs), and ultimately to NeuN+ mature GCs. However, the molecular mechanisms governing these transitions remain poorly understood. Here, we demonstrate that Sin3A, a core component of the histone deacetylase (Hdac) complex, plays a sequentially essential role in driving GC lineage progression across distinct precursor stages. In Sox2+ cells, Sin3A facilitates their transition to GCPs by repressing Sox2 expression. In GCPs, Sin3A suppresses Atoh1 transcriptional activity by recruiting Neurod1 as a co-repressor, thereby promoting GCP differentiation. Additionally, Sin3A ensures the survival and specification of GCPs by repressing non-lineage-specific gene expression. Our findings highlight the central role of the Sin3A complex in orchestrating distinct stages of cerebellar GC lineage development.

overall_design: ChIP-seq of GFP+; mApple- GCPs and GFP-; mApple+ GCPs from the cerebellar tissues of wildtype mice at postnatal day 6

first: Chin

last: Chiang


title: Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycemic control

city: Chicago

first: Zachary

middle: Lee

last: Sebo

address: 303 E Superior St

institute: Northwestern University

summary: Metformin is a therapeutically versatile biguanide drug primarily prescribed for type II diabetes. Despite its extensive use, the mechanisms underlying many of its clinical effects, including attenuated postprandial glucose excursions, elevated intestinal glucose uptake, and increased production of lactate, Lac-Phe and GDF15, remain unclear. Here, we map these and other clinical effects of metformin to intestine-specific mitochondrial complex I inhibition. Using human metabolomic data and an orthogonal genetics approach in male mice, we demonstrate that metformin suppresses citrulline synthesis, a metabolite generated exclusively by small intestine mitochondria, and increases GDF15 by inhibiting the mitochondrial respiratory chain at complex I. This inhibition co-opts the intestines to function as a glucose sink, driving uptake of excess glucose and converting it to lactate and Lac-Phe. Notably, the glucose-lowering effect of another biguanide, phenformin, and berberine, a structurally unrelated nutraceutical, similarly depends on intestine-specific mitochondrial complex I inhibition, underscoring a shared therapeutic mechanism.

overall_design: RNA-seq profiling of mouse jejunum from Vil-Cre and Vil-Cre:NDI1 animals (i.e., cre controls and mice that express Saccharomyces cerevisiae NDI1 in jejunum) to determine if NDI1 expression effects the transcriptome.


title: Comprehensive Funtional Mapping of ADPRylation sites on Gene Regulatory Targets of PARP1 [RNA-Seq]

city: Dallas

first: W. Lee

last: Kraus

address: 5323 Harry Hines Blvd.

institute: UT Southwestern Medical Center

summary: Breast cancer molecular subtypes are based on distinct gene expression patterns. Recently, we described how subtype-specific transcription factors and their cognate enhancers drive the distinct gene expression patterns observed across breast cancer subtypes. As an extension of these studies, we employed a mass spectrometry-based proteomic approach to screen gene regulatory proteins for ADP-ribosylation (ADPRylation) across six breast cancer cell lines representing the luminal and triple-negative subtypes. Using an analog-sensitive PARP1- coupled with mass spectrometry approach, we have identified and catalogued the PARP1 ADPRylated proteome. We find that ADPRylation varies dramatically across the different subtypes of breast cancers.  We hypothesize that ADPRylation of subtype-specific gene regulatory proteins dictates their function and may influence the response of breast cancer cells to PARP inhibitors. Using RNA-seq (T-47D and MDA-MB-468) and ChIP-seq (T-47D) with or without PARP inhibitor (Olaparib) we sought to understand how the ADPRylated proteome drives gene regulation and gene expression in breast cancer. We find that Olaparib treatment modulates the binding activity of certain transcription factors in a subtype-specific manner, thereby regulating the downstream gene expression.

overall_design: Breast cancer cell lines (T-47D and MDA-MB-468) treated with DMSO (control) or Olaparib (PARP1 inhibitor).

first: Minjung

last: Kwon

first: Poulami

last: Tapadar

first: Yangyang

last: Dai

first: Sneh

last: Koul

first: Tulip

last: Nandu

first: Dan

last: Huang

first: Cristel

middle: V

last: Camacho

first: Kraus

last: W Lee


title: Targeting phosphatidylserine for tumor cell suppression [RNA-seq]

status: Public on Aug 05 2026

city: Hangzhou

first: Yixuan

last: Hu

address: No. 600 Dunyu Road,  Xihu District

institute: Westlake University

summary: Alterations in lipid metabolism are frequently observed in cancers, playing a pivotal role in tumor cell survival and proliferation. Phosphatidylserine (PS), the most negatively charged glycerophospholipid in eukaryotic membranes, is synthesized in mammals by key enzymes, such as phosphatidylserine synthase 1 (PTDSS1). Here, we identify a PS-dependent metabolic vulnerability in esophageal squamous cell carcinoma (ESCC) and glioblastoma (GBM). Pharmacological inhibition of PTDSS1 potently suppresses tumor growth with nanomolar efficacy. Mechanistically, PS depletion causes a metabolic depletion of PS and phosphatidylethanolamine (PE), triggering endoplasmic reticulum (ER) stress and activating autophagy. These findings reveal an unrecognized PS-dependent metabolic dependency for tumor cell viability, indicating that targeting PS synthesis may offer a promising therapeutic approach for tumor cell suppression.

overall_design: To examine the transcriptional response to PTDSS1 inhibition, two human cancer cell lines were used: KYSE30 esophageal squamous cell carcinoma cells and U138MG glioblastoma cells. For each cell line, cells were treated with 100 nM PTDSS1 inhibitor for 48 hours; parallel cultures treated with an equal volume of DMSO served as vehicle controls. Three biological replicates were included for both the inhibitor-treated and control conditions in each cell line. Total RNA was extracted from all samples, and high-throughput RNA sequencing was performed to profile gene expression changes induced by PTDSS1 inhibition. Differential expression analysis was conducted to compare the inhibitor-treated group against the vehicle control group within each cell line.

first: Yaqi

last: Cui

first: Zeqiong

last: Xu

first: Duo

last: Wu

first: Xiaochun

last: Yu


title: Effect of zinc supplementation on gene expression of Rhizopus arrhizus NCCPF 710004

status: Public on Dec 02 2025

city: Chandigarh

first: Rachna

last: Singh

state: Chandigarh

address: Department of Microbial Biotechnology, Technology Block, Panjab University (South Campus), Sector 25

department: Microbial Biotechnology

country: India

institute: Panjab University

summary: Rhizopus arrhizus is the predominant causative agent of mucormycosis worldwide. During COVID-19 pandemic, an upsurge of this disease was noted in many countries including India. Many clinical/epidemiological studies reported that the excessive intake of nutritional supplements, especially that of zinc, owing to self-medication and over-prescription, was one of the risk factors for the emergence of Covid-19 associated mucormycosis. However, the experimental evidence remains limited. This study evaluates the changes in gene expression of Rhizopus arrhizus upon culturing under zinc-enriched conditions.

overall_design: mRNA was sequenced from Rhizopus arrhizus NCCPF 710004 after culturing in RPMI-1640 for 6 h without or with 45 µM zinc by Illumina NovaSeq 6000 technology, with 150bp paired end reads.

first: Anjna

last: Kumari

first: Pavneet

last: Kaur

first: Jasdeep


title: Effect of CAMK2D inhibition in RBM20 loss of function mouse models

status: Public on Dec 01 2025

city: Heidelberg

first: Maarten

last: van den Hoogenhof

state: (select)

address: In Neuenheimer Feld 669

country: Germany

institute: Institute of Experimental Cardiology

summary: Mutations in RBM20, a splicing factor that targets multiple pivotal cardiac genes including TTN and CAMK2D, cause a clinically aggressive form of dilated cardiomyopathy (DCM) with a high risk of malignant ventricular arrhythmias. We hypothesized that the RBM20 target CAMK2D contributes critically to RBM20 cardiomyopathy. Here, we sequenced the hearts of Rbm20/Camk2d double knockout mice, as well as the hearts of Rbm20-R636Q knock-in mice treated with the CAMK2 inhibitor Hesperadin.

overall_design: RNAseq of RBM20/CAMK2D double knockout mice and RBM20-R636Q knock-in mice with CAMK2 inhibition using Hesperadin


title: Stable inheritance of the Streptomyces linear plasmid SCP1 by dual ParABS partition systems [SCP1_PCN]

city: Norwich

first: Leah

last: McPhillips

address: Colney Lane

department: Molecular microbiology

country: United Kingdom

institute: John Innes Centre

summary: Low copy number plasmids must encode maintenance mechanisms, such as partitioning systems, to ensure that the plasmid is sustained through host generations. Plasmid partition systems segregate sister plasmid copies and are subdivided into different types based on the NTPase they encode. The characterisation and distribution of partition system types is well understood in Enterobacteriaceae plasmids. However, how these systems maintain plasmids and are distributed across wider bacterial diversity is poorly understood. We searched a large and diverse plasmid database to identify the distribution of partition system types and found that plasmids encoding multiple partition systems are more widespread than previously realised, composing ~19% of all plasmids predicted to encode partition systems. Many of these plasmids were predicted to encode multiple partition systems of the same type, which had never been studied previously. We used the Streptomyces coelicolor A3(2) plasmid SCP1, which encodes two type Ia partition systems, as a model to investigate this. Sequence analysis of the SCP1 partition systems revealed that both ParB proteins contain less conserved CTP-binding pockets, suggesting one or both proteins may not behave like canonical ParB proteins. However, using a combination of chromatin immunoprecipitation with deep sequencing (ChIP-seq), biochemistry and mutagenesis we show that both ParB proteins behave like bone fide ParB proteins: they bound to distinct parS sites on SCP1, both proteins bound and hydrolysed CTP and both proteins required CTP and their cognate parS site to accumulate, or spread, on DNA. Intriguingly, however, only ParB1 was critical for SCP1 stability. Together, our findings further our understanding of Streptomyces plasmid maintenance by providing the first functional characterisation of two type Ia partition systems coexisting on a single plasmid and offer new insights into the diversity and distribution of plasmid partition systems.

overall_design: To determine the plasmid copy number per chromosome of the two plasmids of Streptomyces coelicolor A3(2), the wild type strain was grown on solid soya flour mannitol (SFM) agar until visably sporeulated. Spores were harvested and the genomic DNA was extracted from these spores and sequenced in order to determine what the plasmid copy number was compared to the chromosome. Spores were chosen over vegetative mycelium as they are metabolically inactive and therefore should represent the true ratio of the plasmid copy number per spore, as during vegetative growth differences in the replication rate of these genetic elements could artifically inflate/deflate the true plasmid copy number ratio to the chromosome.

first: Tung

last: Le


title: Stable inheritance of the Streptomyces linear plasmid SCP1 by dual ParABS partition systems [ChIP-Seq]

summary: Low copy number plasmids must encode maintenance mechanisms, such as partitioning systems, to ensure that the plasmid is sustained through host generations. Plasmid partition systems segregate sister plasmid copies and are subdivided into different types based on the NTPase they encode. The characterisation and distribution of partition system types is well understood in Enterobacteriaceae plasmids. However, how these systems maintain plasmids and are distributed across wider bacterial diversity is poorly understood. We used the Streptomyces coelicolor A3(2) plasmid SCP1, which encodes two type Ia partition systems, as a model to investigate this. Sequence analysis of the SCP1 partition systems revealed that both ParB proteins contain less conserved CTP-binding pockets, suggesting one or both proteins may not behave like canonical ParB proteins. However, using a combination of chromatin immunoprecipitation with deep sequencing (ChIP-seq) we demonstrate that both the SCP1 ParB proteins, ParB1 and ParB2, bound to distinct parS sites on SCP1, and accumulate, or spread, on DNA approximately 20 kb away from their initial parS loading site. Together, our findings further our understanding of Streptomyces plasmid maintenance by providing the first functional characterisation of two type Ia partition systems coexisting on a single plasmid and offer new insights into the diversity and distribution of plasmid partition systems.

overall_design: ChIP-seq experiment to determine the DNA-binding sites of the ParB1 and ParB2 proteins of the linear plasmid SCP1 in its host, Streptomyces coelicolor A3(2). ParB1-3xFLAG and ParB2-3xFLAG were constructed by inserting 3x-FLAG tags at the 3' ends of the parB1 and parB2 genes at their native loci on the SCP1 plasmid, allowing for detection of the FLAG-tagged proteins under the production of their native promoters using the ReDirect gene editing method which inserts the tag and an apramycin resistance casette.Non-tagged alleles were included as negative controls. Two biological replicates were carried out per strain. Anti-FLAG agarose beads were used for the ChIP experiment.


title: E2F4/SETD1A axis-mediated METTL3 methylation promotes tumor immune evasion through impeding endogenous retroelements expression

city: Wuhan

first: Haijie

last: Li

address: no.1095 Jiefang Avenue

department: Tongji Hospital

institute: Huazhong University of Science and Technology

summary: Colorectal cancer (CRC) progression and recurrence persist as major clinical challenges despite standard therapies. Emerging evidence underscores that tumor relapse arises from crosstalk between malignant cells and the immunosuppressive microenvironment, yet the role of non-histone lysine methylation in this interplay remains unclear. Here, we identify di-methylation of lysine 513 (K513) on methyltransferase-like 3 (METTL3) as a key epigenetic modification associated with CRC progression and recurrence. Mechanistically, we reveal that SETD1A catalyzes METTL3 K513 methylation, enhancing its binding affinity to S-adenosylmethionine (SAM) and augmenting RNA m⁶A deposition. Strikingly, METTL3 methylation suppresses endogenous retroelements expression, leading to impaired type I interferon responses and tumor immune evasion. We further uncover a fluorouracil-induced E2F4/SETD1A/METTL3 regulatory axis, wherein E2F4 self-regulation activates SETD1A to drive METTL3 methylation. Targeting this axis through pharmacological inhibition of E2F4 or genetic disruption of METTL3 methylation synergizes with immune checkpoint blockade (ICB), significantly suppressing tumor growth. Our findings unveil a methylation-dependent regulatory mechanism that reshapes the tumor immune microenvironment, offering a novel therapeutic strategy for CRC.

overall_design: To determine the biological importance of METTL3 methylation at K513, we conducted methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequence on METTL3 WT and K513R LoVo cells


title: Development of CAR T cells Targeting U5 snRNP200 for the Treatment of Acute Myeloid and B-Lymphoid Leukemias

status: Public on Nov 30 2025

city: New York

first: Maxim

last: Maron

state: New York

address: 1275 York Ave

department: Molecular Pharmacology Program

institute: Memorial Sloan Kettering Cancer Center

summary: Developing chimeric antigen receptor (CAR) T cells for acute myeloid leukemia (AML) has been challenging due to a lack of known AML-associated antigens which spare normal hematopoietic precursor cells. Here we reasoned that donor auto-antibodies from AML recipients cured following allogeneic transplant and responsible for graft-versus-leukemia effect could be engineered to create effective CAR-T cells. We generated CAR-T cells against one such antigen - U5 snRNP200, an RNA helicase localized to the surface of AML cells and absent from normal hematopoietic precursors. Anti-U5 snRNP200 CAR T cells were effective in human and syngeneic models of AML as well as B acute lymphoblastic leukemia (B-ALL), a setting where surface U5 snRNP200 was also present. IL-18 armoring augmented target antigen expression due to cell surface trafficking of U5 snRNP200 with CD32A. These data thereby identify a CAR-T cell platform which addresses prior limitations in tumor-selectivity and safety for patients with acute leukemias.

overall_design: We employed Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) and T-cell Receptor Sequencing (TCR-seq) to simultaneously capture gene expression, surface proteomes, and the T-cell receptor repertoire. The  TotalSeq-C Mouse Universal Cocktail (BioLegend) was applied to CD45.1+ endogenous blood cells as well as CD45.2+ RN2 leukemia, donor-derived T, and control or anti-U5 snRNP200 IL18-armored chimeric antigen receptor (CAR) T cells.

first: Takeshi

last: Fujino

first: Omar

last: Abdel-Wahab

first: Anthony

middle: F

last: Daniyan


title: A novel biallelic missense variant in the BTB domain of ZBTB24 leads to Immunodeficiency, Centromeric instability and Facial anomalies type 2 syndrome

city: Napoli

first: Francesco

last: Cecere

state: Napoli

address: Via Posillipo 226

department: UOC Ricerca Clinica e Traslazionale

country: Italy

institute: AORN Santobono-Pausilipon

type: Methylation profiling by genome tiling array

summary: ZBTB24 is a member of a protein family that includes a Broad-Complex, Tramtrack, and Bric a Brac (BTB) domain, which functions in protein-protein interactions. ZBTB24, a transcription factor, binds its targets through its C-terminus zinc finger (ZF) domain. Biallelic ZBTB24 mutations lead to the rare autosomal recessive Immunodeficiency, Centromeric instability and Facial anomalies subtype 2 (ICF2) syndrome. The majority of the ICF2 patients have biallelic loss of function alleles. The remaining patients have missense variants in their ZF domain. As a consequence, one of ZBTB24’s targets, CDCA7, the gene responsible for ICF3, is not expressed in ICF2 patient cells. Similar to all subtypes of ICF syndrome, ZBTB24 pathogenic mutations lead to significant DNA hypomethylation throughout the genome.   Here we describe a patient with a homozygous variant with unknown significance (VUS), p.Val43Leu, in the BTB domain of ZBTB24. To examine the pathogenicity of this change, we determined DNA methylation levels and patterns in patient blood and lymphoblastoid cells (LCLs). We found significant hypomethylation throughout the patient’s genome, with a methylation pattern identical to that of other ICF2 patients, albeit with less severe hypomethylation. Importantly, the satellite repeats were significantly hypomethylated, a hallmark of ICF syndrome. We found that the p.Val43Leu change significantly reduces the protein’s stability, resulting in very low levels of CDCA7 expression in the patient-derived LCLs. Additionally ,the nuclear pattern of localization of ZBTB24 was disrupted due to this amino acid change. Thus, we demonstrate for the first time that biallelic missense variants in the BTB domain of ZBTB24, can disrupt the normal functionality of the protein and lead to ICF2 syndrome.

overall_design: DNA samples extracted from ICF2 patients (RZ, pV and pD) and Control LCLs, as well as RZ patient peripheral whole blood were subjected to methylation analysis using Infinium MethylationEPIC 850K Bead Chip Array. We assessed the methylation levels at both genome-wide and satellite repetitive elements

first: Maria

middle: R

last: Matarazzo

first: Sara

last: Selig

first: Ido

last: Han


title: Postprandial changes to systemic metabolism imprint durable changes to T cell immunity [ATAC-seq]

status: Public on Nov 28 2025

city: Pittsburgh

first: Daniel

last: Kaplan

state: PA

address: 5051 Centre Avenue, 4041

department: Immunology

institute: University of Pittsburgh

summary: Systemic nutrient availability waxes and wanes with dietary input. Here we show that short periods of fasting and refeeding have long-lasting effects on T cell immunity. Human or murine T cells from fed hosts have higher metabolic capacity than those from fasted hosts ex vivo and show better/superior metabolic phenotype and immune response/functions in vitro and in vivo settings of virus infection or tumor model. Serum or chylomicrons enriched from lymphatics of fed mice restores the metabolic and immune functions of fasted T cells. Fed T cells had heightened mTORC1-dependent translation of key immunologic and metabolic genes independent of their epigenetic and transcriptional status. mTORC1 inhibition during the fed period mitigates the postprandial benefit of fed T cells over fasted cells. Our data highlight the need to consider diet content and timing as key factors in immune cell analysis, vaccination strategies, and the generation of cellular therapies.

overall_design: Mice were fasted or fed for overnight (<12 h) and T cells purified. Ex vivo or activated T cells were subjected to epigenetic study/ transcriptomic and translatome studies. For human, blood collected in fasted condition (called as 'Pre') and again after 6 hour of having meal (called as 'Post').  Pre and post ex vivo or activated T cells subjected to transcriptome and translatome studies.

first: Alok

last: Kumar

first: Greg

last: Delgoffe

first: Isha

last: Mehta


title: Postprandial changes to systemic metabolism imprint durable changes to T cell immunity [RNA-seq]


title: Identification of elements driving KIR gene demethylation in CD56-Bright NK cells

city: Frederick

first: Yongmei

last: Zhao

address: Post Office Box B

department: Advanced Biomedical Computational Science

institute: Frederick National Labroatory for Cancer Research

summary: The variegated expression of the KIR family of class I MHC receptors is crucial for the generation of specialized NK cells capable of detecting changes in the expression of specific HLA genes or alleles. Understanding the timing and mechanism of KIR gene activation will lead to improved methods for the generation of fully functional NK cells in vitro. Previous studies revealed that a central RUNX-binding site is a key element required for the demethylation and activation of the KIR proximal promoter. RUNX proteins associate with the TET family of proteins that generate 5‑hydroxymethylcytosine (5hmC) and drive DNA demethylation. We employed a novel system capable of distinguishing 5‑methylcytosine (5mC) and 5hmC residues in DNA to provide insight into the process of KIR gene activation during NK cell development. Significant levels of 5hmC, indicative of TET activity, were observed in variegated KIR genes in CD56Bright NK cells but not the preceding ILCP or subsequent CD56-Dim stages of development. The primary site of 5hmC generation was within the central CREB-binding site, located 11 bp 5' of the consensus RUNX-binding site. Taken together, these findings support a key role of RUNX/TET for KIR gene activation in developing NK cells.

overall_design: 5mC and 5hmC modification was assessed by high throughput DNA sequencing of duet evoC genomic libraries generated from cellular DNA isolated from cells representing four developmental stages: CD34+ hematopoietic progenitor cells (HPC); innate lymphocyte progenitor cells (ILCP); CD56Bright NK; CD56Dim NK.

first: Hongchuan

first: Noah

last: Koenigs

first: Michael

last: Ruesch

first: Olivia

last: Brancato-Buentello

first: Zhonghe

last: Sun

first: Xiongfong

last: Chen

first: Aharon

last: Freud

first: Stephen

middle: K

last: Anderson


title: scRNA-seq transcriptomic profiles of cochlear and vestibular hair cells from adult mice [10_weeks_CBAJ]

status: Public on Nov 25 2025

city: Omaha

first: David

last: He

state: NE

address: 2500 California Plaza

department: Biomedical Science

institute: Creighton University

summary: The cochlear and vestibular sensory epithelia contain four different hair cell (HC) types for detecting sound and motion. There are substantial differences in morphology and function among them. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of HCs in the inner ear.

overall_design: HCs from cochlear and vestibular sensory organs were isolated. cDNA library were constructed using the 10x Genomics Chromium Single Cell 3’ Reagent Kits V3.1.  7 mice were used for each biological replicate, and 6 biological replicates for cochlear sensory epithelium and 4 biological replicates vestibular sensory epithelia were prepared. Illumina NextSeq 6000 sequencer was used for sequencing.

first: Zhenhong

last: Xu

first: Samadhi

last: Kulasooriya

first: Huizhan

last: Liu


title: DNA methylation-based classification of hematolymphoid neoplasms

status: Public on Jan 26 2026

city: Wantirna South

first: Rust

last: Turakulov

state: Victoria

address: u23 105 Mountain Hwy

department: Bioinformatics

country: Australia

institute: AGRF

summary: Accurate pathological diagnosis is crucial for optimal management of cancer patients. For a number of hematolymphoid tumor entities, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter-observer variability in the histopathological diagnosis of many tumor types. Genome-wide DNA methylation profiling has been shown to contribute to accurate and precise tumor classification and diagnosis in several tumor types, including central nervous system neoplasms.  We herein present the development of a comprehensive approach for DNA methylation-based hematolymphoid tumor classification across most entities and age groups and demonstrate its application in a clinical setting, defining 44 methylation classes comprising a good proportion of recognized hematolymphoid tumor types. In several cases, methylation signatures separated recognized tumor types into subclasses that showed statistically significant and distinct patient outcomes.  We validate the classifier in independent samples that were not utilized in classifier development and show that the reliability of this method is highly accurate (concordance 97%) with a substantial impact on diagnostic precision in addition to standard methods.  We show a relationship of methylation class match scores with tumor purity, finding that high-tumor-purity samples are more likely to receive a high-confidence match with our classifier. Finally, we show the impact of the classifier in clinical practice, where classifier results resulted in a change in diagnosis in specific hematolymphoid neoplasms. For broader accessibility, a free and user-friendly online portal for access to the hematolymphoid tumor methylation classifier will be available for external users.

overall_design: The reference set from previously published and inhouse data was used to train classifier. The validation dataset asembled from previously published data and new samples processed inhouse and acquired from collaborators. Classification perfomace estimated on validation dataset.

first: Annapurna

last: Saksena

first: Christin

last: Siewert

first: Omkar

last: Singh

first: Zied

last: Abdullaev

first: Ting

last: Zhou

first: Jeremiah

last: Karrs

first: Drew

last: Pratt

first: Deanna

last: Riley

first: Shannon

last: Skarshaug

first: Valerie

last: Zgonc

first: Lana

last: Sultanaeva

first: Ruifeng

last: Teng

first: Liqiang

last: Xi

first: Andreas

last: von Deimling

first: Martí

last: Duran-Ferrer

first: José

last: Martín-Subero

first: Elias

last: Campo

first: Stefania

last: Pittaluga

first: Mark

last: Raffeld

last: Capper

first: Elaine

middle: S

last: Jaffe

first: Kenneth

last: Aldape


title: Inhibition of ADSS2-mediated de novo AMP biosynthesis resensitizes acute myeloid leukemia to BH3 mimetics [scRNA-seq]

status: Public on Nov 21 2025

city: Monrovia

first: Ling

last: Li

address: 1218 S 5TH AVE, MONROVIA

department: Hem Malignancies Trans Sci

institute: City of Hope National Medical Center

summary: De novo purine synthesis is required to promote tumor growth; however, its role in therapy resistance remains elusive. Here, through a dynamic BH3-priming based CRISPR-Cas9 screen, we found that deletion of ADSS2, which encodes for an enzyme functioning in de novo AMP synthesis, re-sensitizes drug resistant acute myeloid leukemia (AML) cells to BH3 mimetics. Single-cell sequencing and metabolomics analyses reveal that high ADSS2 activity in leukemia samples including those with TP53 aberrations inversely correlates with venetoclax responsiveness. Further, we developed anADSS2 antagonist, exhibiting synergism with BH3 mimetics in preclinical AML models. Mechanistically, sensitization to BH3 mimetics mediated by ADSS targeting was associated with downregulated AMPK activity, which governs mitochondrial homeostasis. AMPK activity in resistant cells promotes mitophagy to eliminate damaged mitochondria upon BH3 mimetics treatment. These data demonstrate that AMP synthesis governs venetoclax resistance, and that combining ADSS targeting with BH3 mimetic treatment could represent a promising approach against AML.

overall_design: We engrafted NSGS mice with primary AML blasts(P9), then treated mice with Venetoclax/Azacitidine  or vehicle until resistance emerged. We next harvested and purified human cells from BM for analysis.

first: Xin

last: He

first: Wei

last: Chen


title: Inhibition of ADSS2-mediated de novo AMP biosynthesis resensitizes acute myeloid leukemia to BH3 mimetics

overall_design: P1-R cells with WT or ADSS2-KO were collected for analysis.


title: Integrated sudden origin of complex N2-fixing cells upon global oxygenation

status: Public on Nov 20 2025

first: Yali

last: Wang

address: NO.152 Luoyu Road

department: School of Life Sciences

institute: Central China Normal University

summary: Origin of a novel organ or specialized cell can be considered as a process by which the underlying gene regulatory network (GRN) was organized. Large changes in this process could be caused by co-option of functional modules to novel locations or re-wiring of the regulatory networks, through alterations in cis-regulatory elements and recruitment of new regulatory factors. Here, we show the role of an evolutionary coordinator in the integrated sudden origin of complex N2-fixing cells in multicellular cyanobacteria, called heterocysts, during the Neoproterozoic Oxygenation Event (NOE). We employed ChIP-seq and a synthetic Anabaena transcription system in Escherichia coli to systematically analyze the gene regulatory relationships. The GRN of heterocyst differentiation (het-GRN) and the ancestral primitive GRN were successfully reconstructed.

overall_design: ChIP-seq of HetZ in wild type and mutant strains (hetZ4-201 and DhetP) of Nostoc sp. PCC 7120 at 8 h after nitrogen stepdown.

first: Xi

last: Hu

first: Xudong

last: Xu


title: Antigen-reactive CD4 T cells after SARS-CoV-2 vaccination show divergent phenotypic states with or without restimulation [separate samples]

status: Public on Nov 19 2025

city: Erlangen

first: Kilian

last: Schober

state: Bavaria

address: Maximiliansplatz 2

department: Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene

institute: Universitätsklinikum Erlangen

summary: Understanding T cell fate requires precise knowledge of antigen reactivity. For CD4+ T cells, conventional identification of antigen reactivity by peptide restimulation relies on cellular activation, but thereby also introduces a phenotypic bias. However, by performing single-cell RNA and TCR sequencing on both antigen-stimulated and unstimulated samples, clonotypes can be tracked across conditions to identify antigen-reactive CD4+ T cells and simultaneously assess their phenotypes in the unperturbed state. Using this “reverse phenotyping” strategy, complemented by DNA-barcoded peptide–HLA class II multimers, we here investigated the longitudinal phenotypic evolution of SARS-CoV-2 spike–reactive CD4+ T cells after repeated mRNA vaccination. Without stimulation, reactive clones showed more Th-neutral features and less of an activated Th1-like state than would be assessed after antigen restimulation, yet retained a distinct transcriptional state into the memory phase. These results uncover durable imprints in antigen-reactive CD4+ T cells and highlight that cell state classification can differ fundamentally when judged by phenotype versus function.

overall_design: Antigen-specific T cells after SARS-CoV-2 mRNA vaccination were identified by in vitro-restimulation using a peptide mix spanning the full-length SARS-CoV-2 spike glycoprotein. In vitro re-stimulated and unstimulated cells (non-naive CD4 and CD8 T cells) were sorted by FACS and subjected to 5' scRNAseq on a 10x Genomics platform

first: Katharina

last: Kocher

first: Felix

last: Drost

first: Christine

last: Schülein

first: Bernd

last: Spriewald

first: Benjamin

last: Schubert


title: RNA-sequencing analysis of tumor tissues from two Drosophila yki variants

city: hangzhou

first: qiaoran

last: li

address: Qinchun Road 79

institute: The First Affiliated Hospital, School of Medicine，Zhejiang University

summary: In this study, we demonstrated that tumor-bearing flies exhibit enhanced avoidance of bitter substances, and it is correlated with the severity of the tumor in our genetic models. To identify tumor-secreted cytokines uniquely upregulated in the malignant tumor model (GMR>ykiSA) compared to the mild tumor model (GMR>ykiWT), we performed RNA-sequencing analysis on both types of yki-induced tumor tissues.

overall_design: 3 samples each for GMR-Gal4 control (duizhao) head tissue and GMR>ykiSA, GMR>ykiWT tumor head tissue were used to extract the RNA. Each sample contains 50-80 heads.

first: Qiaoran

first: Pumin

last: Zhang

first: Benjiang

last: Qiao


title: Canopy1/Cnpy1 is required for proper V2R processing and transport; its functional loss impairs basal/V2R vomeronasal sensory neurons function and circuit organization.

status: Public on Nov 18 2025

city: Albany

first: Paolo

middle: Emanuele

last: Forni

address: 1400 Washington Avenue

department: Biology

institute: University at Albany

summary: The Vomeronasal Organ (VNO) of rodents is populated by different types of Vomeronasal Sensory Neurons (VSNs). Apical VSNs, located near the lumen, express the transcription factor(TF) Meis2, V1R family receptors, and the G protein subunit Gao; the VSNs distributed closer to the basal lamina express the TF Tfap2e/AP-2ε, V2R receptors, and the G protein subunit Gai2. In addition sparse cells in the VNO express  the Formyl Peptide Receptors (FPRs). Single-cell mRNA sequencing (scRNA Seq) identified over 300 differentially expressed genes between these cell types, with many linked to the endoplasmic reticulum (ER). Among these ER proteins, Canopy1 (Cnpy1), was found to be among the most enriched genes in V2R+ VSNs. Only previously studied in zebrafish, Cnpy1 was found to affect Fgfr1 signaling and thus is also known as “FGF signaling regulator-1”. In a previous study we discovered that AP-2e upregulates Cnpy1 expression. Although Cnpy1 knockout mice are viable and have normal VNO development at birth, they experience a progressive degeneration and loss of V2R-expressing VSNs. Before symptoms appear, the basal VSNs of KO mice display reduced V2R protein immunoreactivity in the soma and a complete absence of the protein in the lumen of the VNO, rendering the neurons non-functional. Cnpy1 KOs exhibit altered guidance cues and adhesion molecule expression, along with disrupted connectivity to the accessory olfactory bulb.  Our study shows that distinct neuronal types depend on unique ER protein repertoires to maintain proper proteostasis. The loss of Cnpy1 highlights the importance of cell–type–specific ER factors in the differentiation and function of specific neurons, revealing mechanisms that drive neuronal diversity and vulnerability to ER gene disruption.

overall_design: Whole postnatal vomeronasal organs were dissected from P21 (Cnpy1 KO) C57BL/6J-Cnpy1em1cyagen mice, cells were isolated then analyzed using scRNAseq.

first: Nick

last: Mathias

first: Nikki

last: Dolphin

first: Anthony

last: Ruquet


title: Rerouting phosphoenolpyruvate in sugar-rich tissues enables increased fatty acid biosynthesis

city: Urbana

first: Gabriel

last: Beuchat

email: beuchat2@illinois.edu, beuchag@uw.edu

state: IL

address: 1201 W Gregory Dr

department: Plant Biology

institute: University of Illinois at Urbana Champaign

summary: Metabolic engineering in the vegetative tissues of highly productive C4 crop, such as sugarcane, to produce oil is a promising strategy to convert solar energy into biofuel. However, biofuel production needs to be increased to meet the commercial requirements. To address this challenge, we deployed a novel approach to redirect phosphoenolpyruvate flux into plastids via overexpressing a plastidial phosphoenolpyruvate/phosphate translocator (PPT1). The concept was first tested in Arabidopsis. Excitingly, the results showed overexpressing AtPPT1 boosted fatty acid levels in leaves of sugar-rich sweet11;12;13 mutant rather than in the wild type. Increased fatty acid and oil accumulation were observed in older leaves of the triple mutant rather than in young leaves. Metabolomic analysis revealed that overexpressing AtPPT1 enabled the transition of the glycolytic intermediate metabolites from accumulating in sweet11;12;13 mutant back to a similar level as wild type. Under sugar-rich physiological conditions, overexpressing AtPPT1 triggers systematic transcriptomic changes involving class II trehalose-6P synthase (TPS) mediated signaling pathway, which regulates fatty acid synthesis. The strategy was further confirmed in sugarcane, where overexpressing sorghum SbPPT1 driven by a cane stem-specific promoter boosted fatty acid levels (>20% increase) in mature internodes of transgenic sugarcane plants without leading to obvious growth penalty. Positive correlations were observed between fatty acid level and SbPPT1 expression level. In summary, our work reported that directing phosphoenolpyruvate into plastids of sugar-rich tissues can stimulate fatty acid biosynthesis in vegetative tissues. Our strategy promises to achieve commercial-scale lipid production in engineered sugarcane.

overall_design: Wild Type and Sugar Rich Triple mutant arabidopsis were grown under normal conditions, one set as control and the other overexpressing AtPPT1

first: Jiang

first: Xueyi

last: Xue

first: Michael

last: Tang

first: Viet Dang

last: Cao

first: Timothy

last: Changa

first: Yaxin

last: Li

first: Stephen

middle: P

last: Long

first: Fredy

last: Altpeter

first: Li-Qing

last: Chen


title: Evolutionary remodeling of the ventral retina enables aerial vision in the four-eyed fish Anableps anableps

city: Baton Rouge

first: Patricia

last: Schneider

state: Louisiana

address: LSU 131 Life Sciences Building

department: Biological Sciences

institute: Louisiana State University

summary: The emergence of evolutionary novelties remains a central challenge in biology, particularly for complex organs such as the vertebrate eye. While visual systems have repeatedly undergone degeneration or loss, examples of innovation are rare and poorly understood. Mechanistic insight into such gains requires tractable systems in which novel visual functions have evolved. Here we leverage the four-eyed fish Anableps anableps to uncover the cellular and molecular basis of adaptation to simultaneous aerial and aquatic light. Combining single-nucleus and spatial transcriptomics, we show that the Anableps ventral retina has been developmentally and functionally reconfigured for aerial vision. In fully aquatic teleosts such as zebrafish, ventral photoreceptors are tuned to red-shifted, downwelling light. In contrast, we show that Anableps exhibits an expanded and diversified ventral cone population encompassing ultraviolet-, blue-, green-, and red-sensitive types, enabling broad-spectrum, high-intensity vision from above water. To estimate Anableps opsin spectral properties, we employed OPTICS, a machine-learning model of opsin spectral tuning, which predicts that the ventrally expressed opn1mw2 opsin is red-shifted relative to typical green-sensitive pigments. Analysis of dorsal-ventral patterning markers reveals an overrepresentation of ventral retinal cell types. Consistent with this, comparative spatial transcriptomic profiling of developing and adult Anableps and the killifish (Fundulus heteroclitus) indicates a dorsal displacement of the dorsal-ventral boundary in Anableps, resulting in a proportionally larger ventral retinal domain. Collectively, our results reveal that Anableps achieved its unique dual visual capacity by developmentally expanding and functionally reprogramming the ventral retina for aerial light detection, an evolutionary innovation that redefines how retinal domains can adapt to radically different visual environments.

overall_design: Five biological replicas of retinas from adult Anableps specimens were dissected and minced with a razor blade in a petri dish on ice. The minced tissue was resuspended in 1 mL of lysis buffer (ATAC-seq lysis buffer, Active Motif Inc.) and then homogenized in a pre-chilled Dounce homogenizer (3 strokes). The homogenate was filtered through a 40 µm cell strainer and immediately centrifuged in an Eppendorf Protein LoBind tube at 500 xg at 4 °C for 5 minutes in a swinging bucket rotor. The pellet was quickly washed with 1 mL 1X PBS/0.5 % BSA and then resuspended in 1 mL of 1X PBS/0.5 % BSA. Nuclei were counted using a hemocytometer and then a volume corresponding to 106 nuclei was transferred to a new tube and centrifuged at 500 xg at 4 °C for 5 minutes. Nuclei were fixed and frozen using the Evercode Nuclei Fixation Kit v3 (Parse Biosciences) following the manufacturer’s protocol. Five biological replicates were prepared. Fixed and frozen nuclei were then processed to generate eight RNA-sequencing libraries, using the EvercodeTM WT  v3 Kit following the manufacturer’s protocol.

first: Louise

last: Perez

first: Lina

last: Shi

first: Alyssa

last: Daspit

first: Keyla

last: Pruett

first: Carsyn

last: Smith

first: Anna

last: Prideaux

first: Josane

last: Sousa


title: EZHIP-mediated PRC2 inhibition is required to maintain H3K27me3-dependent imprinting post fertilization

city: Paris

first: Laia

last: Richart

address: 13 Rue Pierre et Marie Curie

department: Developmental Biology

country: France

institute: Institut Curie

summary: Zygote inherits parental genomes with distinct chromatin structure. In eutherian mammals, this asymmetry is seen as crucial for embryonic development notably through its involvement in gene imprinting. Besides the well-established role of DNA methylation for gene imprinting, H3K27me3 has also been shown to mediate a transient form of imprinting in mice. Here, we show that maternal deletion of Ezhip, a negative regulator of PRC2, while increasing the asymmetric distribution of H3K27me3 among the parental genomes at the zygotic stage, in fine, impairs H3K27me3-dependent imprinting and mitigates X Chromosome Inactivation in pre-implantation embryos. We show that EZHIP protein, translated from the maternal pool of RNAs, is present during the first cell divisions post-fertilization. It limits PRC2 enzymatic, avoiding the flattening of H3K27me3 deposition throughout the genome and the equalization of H3K27me3 deposition on the two parental genomes. Our study reveals the necessary inhibition of PRC2 activity post-fertilization for proper development in mice.

overall_design: Single cell/embryo RNA samples were prepared from wt and Ezhip matKO oocytes, 2C embryos, blastocysts, and E6.5 extraembryonic ectoderm to assess the impact of maternal depletion of Ezhip on the early stages of embryonic development.

first: Raphael

last: Margueron

first: Seynabou

last: Diop

first: Katia

last: Ancelin

first: Ambre

last: Petitalot

last: Legoix


title: EZHIP-mediated PRC2 inhibition is required to maintain H3K27me3-dependent imprinting post fertilization [ChIP-Seq]

overall_design: Cut&Run-Seq for H3K27me3 was conducted on wt and Ezhip matKO oocytes, 2C embryos, and blastocysts to assess the impact of maternal depletion of Ezhip on Polycomb function during the early stages of embryonic development.


title: The LUMINIDEPENDENS protein is a general repressor of transcription in Arabidopsis [RNA-Seq 2]

status: Public on Nov 17 2025

city: GIF SUR YVETTE

first: Qingyi

last: Wang

address: 630 rue noeztlin

summary: Genomic integrity is constantly challenged by transcription/replication conflicts, a major source of replication stress and instability across all life forms. While extensive studies have uncovered transcription/replication conflicts resolution mechanisms in animals, yeast, and prokaryotes, their counterparts in plants remain largely unexplored. Through a forward genetic screen, we identified the LUMINIDEPENDENS (LD) protein, previously known for regulating the flowering repressor FLC, as a key player in mitigating replication stress in plants. Strikingly, transcriptomic analyses reveal that loss of LD results in the upregulation of over 13,000 genes, establishing LD as a global transcriptional repressor. Consistent with this role, LD binds a substantial portion of the Arabidopsis genome and interacts with the MED18 subunit of the Mediator complex to modulate RNA polymerase II phosphorylation. These findings uncover a fundamental function of LD in fine-tuning transcription genome-wide, with an additional role in suppressing transcription/replication conflicts by locally dampening transcription and promoting replication fork progression. Our work highlights a previously unrecognized genome-protective strategy in plants, opening new avenues for understanding transcription/replication conflict management in eukaryotic systems.

overall_design: The experimental design integrates two spike-in RNA-seq datasets (Dataset1: Arabidopsis thaliana 7-day-old plantlets of Col0, fld, and ld mutants; Dataset2: Col0, pol2a, ld, and ld pol2a mutants) and a classic RNA-seq dataset (shoot apices of Col0, ld, pol2a, and ld pol2a mutants), each with three biological replicates.

first: Clara

last: Bergis-Ser

first: Xiaoning

last: He

first: Maherun

last: Nisa

first: Vickie

last: Kaiser

first: Christelle

last: Mazubert

first: Jeannine

last: Drouin-Wahbi

first: Rim

last: Brik-Chaouche

first: Layla

last: Chmaiss

first: Jeele

last: Van Leene

first: Geert

last: de Jaeger

first: Jose

last: Gutierrez-Marcos

first: Catherine

last: Bergounioux

last: Richet-Bourbousse

first: David

last: Latrasse

first: Moussa

last: Benhamed

first: Cécile

last: Raynaud


title: The LUMINIDEPENDENS protein is a general repressor of transcription in Arabidopsis [LD ChIP-Seq]

last: Wang

overall_design: ChIP-seq samples from Arabidopsis thaliana whole plantlets of the Id mutant genotype expressing the pLD-LD-GFP fusion protein, with two biological replicates and their corresponding input controls. These samples aim to investigate the LD-GFP DNA binding under the Id mutant background. The design also incorporates RNA polymerase II phosphorylation states (S2P and SSP) and histone H3K9ac modification profiles in both wild-type (Col-0) and Id mutant genotypes, with input controls and replicates for each condition.


title: Conserved roles of GATA4 and its target gene TBX2 in regulation of human cardiogenesis

status: Public on Nov 16 2025

city: Cardiff

first: Peter

last: Kille

state: Caerdydd

address: The Sir Martin Evans Building, Museum Avenue

department: School of Biosciences

institute: Cardiff University

summary: The transcription factor (TF) GATA4 is a key mediator of cardiogenesis. GATA4 regulates cardiogenesis through the expression of its target genes, only some of which have been identified. We have used a gain of function model based on pluripotent embryonic ectoderm explants from Xenopus embryos expressing GATA4, to identify a set of downstream targets of GATA4 which are also regulated by Nodal, a known cardiogenic signal. GATA4 was shown to be required for the expression of target genes Tbx2 and Prdm1 in vivo, likely acting in a direct fashion by interacting with their regulatory regions. In addition, Tbx2 and Prdm1 are shown to have roles of their own in vivo, as downregulation of Tbx2, a positive target, and overexpression of Prdm1, a negative target, interferes with cardiac development in Xenopus embryos.  The conservation of the GATA4-TBX2-PRDM1 regulatory relationship was shown in human iPSC-derived cardiomyocytes. Loss of function of GATA4 lead to downregulation of TBX2, upregulation of PRDM1 expression and failure of cardiogenesis. GATA4 deficient cells failed to form normal cardiomyocytes, with most cells likely adopting alternative fates such as smooth muscle cells and fibroblasts, and only a small minority expressing an aberrant cardiomyocyte phenotype.  Genome wide transcriptomic analysis documented severe reduction of cardiomyocyte and endothelial cell transcriptomes and upregulation of transcriptional profiles of smooth muscle cells and fibroblasts. Disruption of TBX2 function did not alter cardiomyocyte differentiation efficiency but led to the formation of abnormal, hypertrophic cardiomyocytes, characterised by defective sarcomeres and upregulation of cardiomyocyte Gene Ontology terms. In addition, we show that PRDM1 is not essential for formation of cardiomyocytes, implying suppression of alternative fates and fine-tuning the expression of the cardiomyocyte program.  The results presented establish a conserved regulatory relationship between GATA4 and its target genes TBX2 and PRDM1, expanding the cardiac GRN and providing further insight into how cardiogenesis proceeds

overall_design: This data set represents RNAseq data from WT and CRISPR-Cas9 manipulated human iPSC cells lines differentiated to represent cardiomyocytes. Genee diting was performed to generate homozygous GATA (GATA4 -/- ), PRDM1 (PRDM1-/-) or  TBX2 (Tbx2del/del). Time and batch matched controls were used for the analsyis.

first: Branko

last: Latinkic

first: Nick

middle: D

last: Owens

first: Michael

last: Gilchrist

first: Ewan

last: Fowler

first: Ilya

last: Patrushev

first: Pavel

last: Kirilenko

first: Nicola

last: Graham