Development and pan-cancer validation of an epigenetics-based random survival forest model for prognosis prediction and drug response in OS DOI Creative Commons

Chaoyi Yin,

K.-H. Chi, Zhiqing Chen

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

Background Osteosarcoma (OS) exhibits significant epigenetic heterogeneity, yet its systematic characterization and clinical implications remain largely unexplored. Methods We analyzed single-cell transcriptomes of five primary OS samples, identifying cell type-specific features their evolutionary trajectories. An epigenetics-based Random Survival Forest (RSF) model was constructed using 801 curated factors validated in multiple independent cohorts. Results Our analysis revealed distinct states the microenvironment, with particular activity cells osteoclasts. The RSF identified key predictive genes including OLFML2B, ACTB, C1QB, demonstrated broad applicability across cancer types. Risk stratification therapeutic response patterns, low-risk groups showing enhanced sensitivity to traditional chemotherapy drugs while high-risk responded better targeted therapies. Conclusion demonstrates excellent prognostic accuracy (AUC>0.997 internal validation, 0.832–0.929 external cohorts) provides a practical tool for treatment stratification. These findings establish clinically applicable framework personalized therapy selection patients.

Language: Английский

Spatial transcriptomic characterization of a Carnegie stage 7 human embryo DOI
Lina Cui, Sirui Lin, Xiaolong Yang

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Language: Английский

Citations

3
CellPhoneDB v5: inferring cell–cell communication from single-cell multiomics data DOI
Kevin Troulé, Robert Petryszak, Batuhan Çakır

et al.

Nature Protocols, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Language: Английский

Citations

3
Single-cell analysis unveils cell subtypes of acral melanoma cells at the early and late differentiation stages DOI Creative Commons

Mengyuan Hou,

Zhijie Zhao,

Songbai Zhu

et al.

Journal of Cancer, Journal Year: 2024, Volume and Issue: 16(3), P. 898 - 916

Published: Dec. 31, 2024

Background: Melanoma, a malignant neoplasm originating from melanocytes, is form of skin cancer with rapidly increasing global incidence, often exacerbated by UV radiation [1].Particularly, acral melanoma, characterized its swift metastasis and poor prognosis, underscores the significance further research into heterogeneity.Single-cell sequencing has been widely utilized in study tumor heterogeneity; however, related to melanoma remains be refined. Materials Methods:We employed single-cell RNA (scRNA-seq) transcriptomic analysis delve cells six samples patients.This approach enabled identification critical cell subpopulations their roles progression.Subsequently, we examined interactions among these analyzed other types.Results: Our identified C3 ID2+ as an early-stage subpopulation C4 PCLAF+ late-stage evolution.Through our analysis, Melanoma significant (AM), playing pivotal role differentiation development AM.Further transcription factors, enriched pathways, stemness, trajectories highlighted (AM) proliferation. Conclusion:This identifies new factors influencing progression, providing foundation for subsequent research.

Language: Английский

Citations

11
Spotiphy enables single-cell spatial whole transcriptomics across an entire section DOI Creative Commons
Jiyuan Yang, Ziqian Zheng, Yun Jiao

et al.

Nature Methods, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization gene expression within whole-tissue sections, but current approaches remain plagued challenge achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome images. delivers most precise cellular proportions in extensive benchmarking evaluations. Spotiphy-derived inferred profiles reveal astrocyte and disease-associated microglia regional specifications Alzheimer’s disease healthy mouse brains. identifies multiple spatial domains alterations tumor–tumor microenvironment interactions human breast data. bridges information gap enables cell localization transcriptomic throughout entire offering highly informative outputs an innovative analysis pipeline for exploring complex biological systems.

Language: Английский

Citations

1
Self-organization of mouse embryonic stem cells into reproducible pre-gastrulation embryo models via CRISPRa programming DOI Creative Commons
Gerrald A. Lodewijk, Sayaka Kozuki,

Clara Han

et al.

Cell stem cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Adventitial fibroblasts direct smooth muscle cell-state transition in pulmonary vascular disease DOI Creative Commons
Slaven Crnković,

Helene Thekkekara Puthenparampil,

Shirin Mulch

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: April 10, 2025

Background: Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs). Mechanisms driving the transition to diseased phenotype remain elusive. Methods: We combined transcriptomic proteomic profiling with phenotypic characterization of source-matched from healthy controls individuals idiopathic arterial hypertension (IPAH). Bidirectional cellular crosstalk was examined using direct indirect co-culture models, responses were assessed via transcriptome analysis. Results: PASMC PAAF undergo distinct shifts during remodeling, limited shared features, such as reduced mitochondrial content hyperpolarization. IPAH-PASMC exhibit increased glycosaminoglycan production downregulation contractile machinery, while IPAH-PAAF display hyperproliferative phenotype. identified in extracellular matrix components, including laminin collagen, alongside pentraxin-3 hepatocyte growth factor, potential regulators transitions mediated PAAF. Conclusions: While PASMCs PAAFs retain their core identities, they acquire disease-associated states. These findings provide new insights into dynamic interplay mesenchymal disease pathogenesis. Funding: This work supported Cardio-Pulmonary Institute EXC 2026 390649896 (GK) Austrian Science Fund (FWF) grant I 4651-B (SC).

Language: Английский

Citations

1
Helicobacter pylori infection promotes M1 macrophage polarization and gastric inflammation by activation of NLRP3 inflammasome via TNF/TNFR1 axis DOI Creative Commons
Fei Xiao, Sihai Chen,

Leyan Li

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 6, 2025

Macrophages play a crucial role in chronic gastritis induced by the pathogenic Helicobacter pylori (H. pylori) infection. NLRP3 inflammasome has emerged as an important component of inflammatory processes. However, molecular mechanism which H. infection drives and macrophages activation remains unclear. Human tissues were collected for clinical significance NLRP3. Infection with was performed using vitro vivo models. Bone marrow-derived (BMDMs) from wild-type (WT), Nlrp3-knockout (KO) Tnfr1-KO mice infected pylori. Western blotting, qRT-PCR, immunofluorescence, immunohistochemistry ELISA utilized functional mechanistic studies. Single-cell RNA sequencing (ScRNA-seq) analysis human gastric tissues, followed validation, indicated that primarily expressed myeloid cells significantly increased pylori-positive compared to pylori-negative gastritis. PMSS1 NCTC11637 strains (THP1 cells) insulin-gastrin (INS-GAS) transgenic mouse model. Deletion BMDMs showed marked inhibition pylori-induced M1 macrophage polarization. Furthermore, upon TNFα, or stimulation, partially blocked TNFα/TNFR1 signaling inhibitors. TNFR1 impaired This study revealed inflammasome, regulated TNF/TNFR1 axis, is key regulator

Language: Английский

Citations

1
Spatial Transcriptomic Analysis Identifies Epithelium-Macrophage Crosstalk in Endometriotic Lesions DOI Creative Commons
Gregory W. Burns, Zhen Fu, Erin L. Vegter

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(2), P. 111790 - 111790

Published: Jan. 10, 2025

Language: Английский

Citations

1
Glycoprotein 130 Antagonism Counteracts Metabolic and Inflammatory Alterations to Enhance Right Ventricle Function in Pulmonary Artery Banded Pigs DOI Creative Commons
Jenna B. Mendelson,

Jacob D. Sternbach,

Ryan Moon

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Right ventricular dysfunction (RVD) is a risk factor for death in multiple cardiovascular diseases, but RV-enhancing therapies are lacking. Inhibition of glycoprotein-130 (GP130) signaling with the small molecule SC144 improves RV function rodent RVD via anti-inflammatory and metabolic mechanisms. However, SC144's efficacy molecular effects translational large animal model unknown. 4-week-old castrated male pigs underwent pulmonary artery banding (PAB). After 3 weeks, PAB were randomized into 2 groups (daily injections [2.2 mg/kg, PAB-SC144, n =5] or vehicle [PAB-Veh, weeks). Five age-matched served as controls. Cardiac MRI quantified size/function. heart catheterization evaluated hemodynamics. Single-nucleus RNA sequencing delineated cell-type specific changes between experimental groups. Electron microscopy mitochondrial morphology. Phosphoproteomics identified dysregulated kinases. Lipidomics metabolomics lipid species metabolites tissue. Quantitative proteomics examined protein regulation. significantly improved ejection fraction (Control: 60±4%, PAB-Veh: 22±10%, PAB-SC144: 37±6%) despite similar afterload. demonstrated PAB-Veh had lower cardiomyocyte higher macrophage/lymphocyte/pericyte/endothelial cell abundances compared to control, many these blunted by SC144. combatted downregulation genes induced PAB. Kinome enrichment analysis suggested counteracted mTORC1 activation. Correspondingly, rebalanced autophagy pathway proteins Integrated lipidomics, metabolomics, analyses revealed restored fatty acid metabolism. Finally, CellChat pericyte-endothelial cross-talk. GP130 antagonism blunts elevated immune abundance, reduces pro-inflammatory gene transcription macrophages lymphocytes, rebalances preserves metabolism cardiomyocytes, restores endothelial pericyte communication improve function.

Language: Английский

Citations

1
Deconvolution and inference of spatial communication through optimization algorithm for spatial transcriptomics DOI Creative Commons
Zedong Wang, Yi Liu,

Xiao Chang

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 14, 2025

Language: Английский

Citations

1