Tissue macrophages reside in anatomically distinct subtissular niches that shape their identity and function. In white adipose tissue (WAT), we identified three macrophage populations with distinct localization, turnover, and phenotypes. Septal adipose tissue macrophages (sATMs), marked by CD209b and lymphatic vessel endothelial hyaluronan receptor 1, were long-lived and positioned in close proximity to adipocyte stem cells (ASCs) within the WAT septum.
View Article and Find Full Text PDFObjectives: We studied individuals who remained uninfected by SARS-CoV-2 despite repeated exposures during a May-July 2020 dormitory outbreak in Singapore.
Methods: We compared immune profiles of those with exposed seronegative (ESN) (negative PCR and serology), with non-infected and infected groups. Following the lifting of quarantine, incident infection rates were compared between the ESN and non-infected cohorts.
Background: Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) collectively represent the majority of dementia cases worldwide. While these subtypes share clinical, genetic, and pathological features, their transcriptomic similarities and differences remain poorly understood.
Methods: We applied single-nucleus RNA-sequencing (snRNA-seq) to prefrontal cortex samples from individuals with non-cognitive impairment control (NCI), and dementia subtypes (AD, DLB, and PDD) to investigate cell type-specific gene expression patterns and pathways underlying pathological similarities and differences across dementia subtypes.
Background: Fine particulate matter (PM) is linked to early-onset cardiovascular disease (CVD); however, the corresponding disease burden has not been assessed. This study aims to evaluate the global, regional, and national early-onset CVD burden attributable to PM from 1990 to 2021.
Methods: We calculated the number, age-standardized rate, and percentage of CVD deaths and disability-adjusted life-years (DALYs) attributable to PM among individuals aged 25-49 years from 1990 to 2021 based on the Global Burden of Disease Study 2021.
Marfan syndrome (MFS) is a genetic disorder primarily impacting the cardiovascular system, eyes, and skeletal structure, with its root cause being mutations in the FBN1 gene. The condition is notably associated with risks such as aortic aneurysm and aortic dissection, which largely drive mortality among those affected. However, the clinical presentation of MFS varies widely, and the link between specific genetic mutations and clinical symptoms is not straightforward.
View Article and Find Full Text PDFGenomics Proteomics Bioinformatics
August 2025
The integration of single-cell multi-omics datasets is critical for deciphering cellular heterogeneities. Mosaic integration, the most general integration task, poses a greater challenge regarding disparity in modality abundance across datasets. Here, we present Align and CompletE (ACE), a mosaic integration framework that assembles two types of strategies to handle this problem: modality alignment-based strategy (ACE-align) and regression-based strategy (ACE-spec).
View Article and Find Full Text PDFBackground: Steatotic liver disease-related hepatocellular carcinoma (SLD-HCC), a rising global challenge, is characterised by unique tumour microenvironment (TME) adaptations.
Objective: This study investigates the immune microenvironment and interactions driving immunosuppression and potential resistance to immunotherapy in SLD-HCC.
Design: We employed single-cell transcriptomics, cytometry by time-of-flight (CyTOF) and two independent spatial transcriptomics platforms to study the TME of 22 SLD-HCC and 31 non-SLD-HCC cases.
Brief Bioinform
May 2025
Spatial omics technologies, generating high-throughput and multimodal data, have necessitated the development of advanced data integration methods to facilitate comprehensive biological and clinical treatment discoveries. Based on the cross-attention concept, we developed an AI learning based toolchain called StereoMM, a graph based fusion model that can incorporate omics data such as gene expression, histological images, and spatial location. StereoMM uses an attention module for omics data interaction and a graph autoencoder to integrate spatial positions and omics data in a self-supervised manner.
View Article and Find Full Text PDFInt J Mol Sci
February 2025
In the original publication, there was a mistake in Figure 2C as published [...
View Article and Find Full Text PDFAlzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance in the immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore the effects of both active and passive Aβ immunization in the AD brain.
View Article and Find Full Text PDFBackground: There is little data about the prognostic value of mitral annular dilatation (MAD) in patients with symptomatic severe aortic regurgitation (AR) undergoing transcatheter aortic valve replacement (TAVR). This study aimed to assess the prognosis value of computed tomography (CT)-determined MAD in such patients.
Methods: Consecutive patients with symptomatic severe AR who underwent pre-TAVR CT between May 2014 and May 2023 were included in this study.
Background: Transcatheter tricuspid valve intervention (TTVI) has demonstrated safety and efficacy in treating high-risk patients with tricuspid regurgitation (TR). The authors aimed to perform a meta-analysis based on reconstructed time-to-event data to compare the clinical benefit of TTVI with medical therapy (MED).
Methods: A systematic literature search was conducted in major databases, including PubMed, Embase, and the Cochrane Library, until 20 October 2023.
Nucleic Acids Res
January 2025
Single-cell RNA sequencing (scRNA-seq) has emerged as the key technique for studying transcriptomics at the single-cell level. In our previous work, we presented the DISCO database (https://www.immunesinglecell.
View Article and Find Full Text PDFThe incidence of large bone defects caused by traumatic injury is increasing worldwide, and the tissue regeneration process requires a long recovery time due to limited self-healing capability. Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration. Inspired by bioelectricity, electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix, thereby accelerating bone regeneration.
View Article and Find Full Text PDFNat Methods
November 2024
Clin Interv Aging
September 2024
Purpose: Transcatheter aortic valve replacement (TAVR) induced coronary artery obstruction (CAO) is a rare but devastating complication. Current preventive strategies need additional procedures and may be associated with adverse events. This study aimed to evaluate the early safety and efficacy of stand-alone TAVR using the J-Valve (Jianshi JieCheng Medical Technology Co.
View Article and Find Full Text PDFAppl Environ Microbiol
October 2024
The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag-RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains.
View Article and Find Full Text PDFThe ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag-RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains.
View Article and Find Full Text PDFRev Cardiovasc Med
December 2023
Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening cardiovascular disorder lacking effective clinical pharmacological therapies. The underlying molecular mechanisms of TAAD still remain elusive with participation of versatile cell types and components including endothelial cells (ECs), smooth muscle cells (SMCs), fibroblasts, immune cells, and the extracellular matrix (ECM). The main pathological features of TAAD include SMC dysfunction, phenotypic switching, and ECM degradation, which is closely associated with inflammation and immune cell infiltration.
View Article and Find Full Text PDFezSingleCell is an interactive and easy-to-use application for analysing various single-cell and spatial omics data types without requiring prior programing knowledge. It combines the best-performing publicly available methods for in-depth data analysis, integration, and interactive data visualization. ezSingleCell consists of five modules, each designed to be a comprehensive workflow for one data type or task.
View Article and Find Full Text PDFNat Methods
September 2024
Advances in spatial omics technologies now allow multiple types of data to be acquired from the same tissue slice. To realize the full potential of such data, we need spatially informed methods for data integration. Here, we introduce SpatialGlue, a graph neural network model with a dual-attention mechanism that deciphers spatial domains by intra-omics integration of spatial location and omics measurement followed by cross-omics integration.
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