Biological data visualization is challenged by the growing complexity of datasets. Traditional single-data plots or simple juxtapositions often fail to fully capture dataset intricacies and interrelations. To address this, we introduce "cross-layout," a novel visualization paradigm that integrates multiple plot types in a cross-like structure, with a central main plot surrounded by secondary plots for enhanced contextualization and interrelation insights.
View Article and Find Full Text PDFExpansion microscopy (ExM) is an innovative super-resolution imaging technique that utilizes physical expansion to magnify biological samples, facilitating the visualization of cellular structures that are challenging to observe using traditional optical microscopes. The fundamental principle of ExM revolves around employing a specialized hydrogel to uniformly expand biological samples, thereby achieving super-resolution imaging under conventional optical imaging conditions. This technology finds application not only in various biological samples such as cells and tissue sections, but also enables super-resolution imaging of large biological molecules including proteins, nucleic acids, and metabolite molecules.
View Article and Find Full Text PDFImaging mass cytometry (IMC) permits high-dimensional single-cell spatial proteomics by harnessing mass tags to replace conventional fluorescence tags. However, the current IMC technique commonly adopts metal-chelated polymer (MCP) tags, which are limited in sensitivity, multiplicity and data acquisition speed. Here, we demonstrate nanometal-organic framework (NMOF) tags, which could concurrently augment IMC's sensitivity, multiplicity, and acquisition speed.
View Article and Find Full Text PDFGenomics Proteomics Bioinformatics
October 2024
Integrin genes are widely involved in tumorigenesis. Yet, a comprehensive characterization of integrin family members and their interactome at the pan-cancer level is lacking. Here, we systematically analyzed integrin family in approximately 10,000 tumors across 32 cancer types.
View Article and Find Full Text PDFTo explore the feature of cancer cells and tumor subclones, we analyzed 101,065 single-cell transcriptomes from 12 colorectal cancer (CRC) patients and 92 single cell genomes from one of these patients. We found cancer cells, endothelial cells and stromal cells in tumor tissue expressed much more genes and had stronger cell-cell interactions than their counterparts in normal tissue. We identified copy number variations (CNVs) in each cancer cell and found correlation between gene copy number and expression level in cancer cells at single cell resolution.
View Article and Find Full Text PDFPort J Card Thorac Vasc Surg
February 2024
Introduction: Popliteal artery aneurysms (PAA) can be very challenging, especially in cases of very large PAAs, with a minimal number of case reports published in the literature.
Methods: This is a case report of a 68-year-old male patient with hypertension, hyperlipidemia, diabetes, and schizophrenia who was found to have a giant (10x8x6cm) partially thrombosed PAA, treated with interposition polytetrafluoroethylene (PTFE) graft via a posterior approach.
Results: Under general anesthesia, the patient was placed in a prone position, and an extended lazy "S" incision was made on the popliteal fossa.
Lead is a widespread environmental hazard that can adversely affect multiple biological functions. Blood cells are the initial targets that face lead exposure. However, a systematic assessment of lead dynamics in blood cells at single-cell resolution is still absent.
View Article and Find Full Text PDFMass cytometry by time-of-flight (CyTOF), a high-dimensional single-cell analysis platform, detects up to 50 biomarkers at single-cell resolution. However, CyTOF analysis of biological samples with a minimal number of available cells or rare cell subsets remains a major technical challenge due to the extensive loss of cells during cell recovery, staining, and acquisition. Here, we introduce a platinum-chimeric carrier cell strategy for mass cytometry profiling of ultratrace cell samples.
View Article and Find Full Text PDFMesenchymal stem/Stromal cells (MSCs) have great therapeutic potentials, and they have been isolated from various tissues and organs including definitive endoderm (DE) organs, such as the lung, liver and intestine. MSCs have been induced from human pluripotent stem cells (hPSCs) through multiple embryonic lineages, including the mesoderm, neural crest, and extraembryonic cells. However, it remains unclear whether hPSCs could give rise to MSCs in vitro through the endodermal lineage.
View Article and Find Full Text PDFUnlabelled: Although many methods have been developed to explore the function of cells by clustering high-dimensional (HD) single-cell omics data, the inconspicuously differential expressions of biomarkers of proteins or genes across all cells disturb the cell cluster delineation and downstream analysis. Here, we introduce a hashing-based framework to improve the delineation of cell clusters, which is based on the hypothesis that one variable with no significant differences can be decomposed into more diversely latent variables to distinguish cells. By projecting the original data into a sparse HD space, fly and densefly hashing preprocessing retain the local structure of data, and improve the cluster delineation of existing clustering methods, such as PhenoGraph.
View Article and Find Full Text PDFTransposable elements (TEs) are abundant in metazoan genomes and have multifaceted effects on host fitness. However, the mechanisms underlying the functions of TEs are still not fully understood. Here, we combine Hi-C, ATAC-seq, and ChIP-seq assays to report the existence of multimegabase supersized loop (SSL) clusters in the Xenopus tropicalis sperm.
View Article and Find Full Text PDFSpatial omics is a rapidly evolving approach for exploring tissue microenvironment and cellular networks by integrating spatial knowledge with transcript or protein expression information. However, there is a lack of databases for users to access and analyze spatial omics data. To address this limitation, we developed Aquila, a comprehensive platform for managing and analyzing spatial omics data.
View Article and Find Full Text PDFRNA N-methyladenosine (mA) is the most abundant internal mRNA modification and forms part of an epitranscriptomic system that modulates RNA function. mA is reversibly catalyzed by specific enzymes, and those modifications can be recognized by RNA-binding proteins that in turn regulate biological processes. Although there are many reports demonstrating mA participation in critical biological functions, this exploration has mainly been conducted through the global KO or knockdown of the writers, erasers, or readers of mA.
View Article and Find Full Text PDFActivator Protein 2 gamma (AP-2γ) is a master transcription factor that plays a critical role in the development and progression of breast cancer. However, the underlying mechanism is still unclear. Herein, using a proteomics approach, we identified Tripartite motif-containing 37 (TRIM37) as a novel coactivator of AP-2γ-mediated transcription in breast cancer cells.
View Article and Find Full Text PDFAndrogen receptor (AR) is a master transcription factor that drives prostate cancer (PCa) development and progression. Alterations in the expression or activity of AR coregulators significantly impact the outcome of the disease. Using a proteomics approach, we identified the tripartite motif-containing 33 (TRIM33) as a novel transcriptional coactivator of AR.
View Article and Find Full Text PDFEarlier detection of biomarkers responsible for cancer relapse facilitates more rational cancer treatment regimens to be designed. Herein, we develop a mass cytometry-based strategy for unbiased mining of cell subsets that potentially contribute to cancer recurrence through panoramic examination of the immunophenotypic features and multidrug resistance characteristics. The incorporation of metal tags enables multiplexed information of single cells to be interrogated based on metal fingerprint.
View Article and Find Full Text PDFHuman pancreatic ductal adenocarcinoma (PDAC) harboring one KRAS mutant allele often displays increasing genomic loss of the remaining wild-type (WT) allele (known as LOH at KRAS) as tumors progress to metastasis, yet the molecular ramification of this WT allelic loss is unknown. In this study, we showed that the restoration of WT KRAS expression in human PDAC cell lines with LOH at KRAS significantly attenuated the malignancy of PDAC cells both in vitro and in vivo, demonstrating a tumor-suppressive role of the WT KRAS allele. Through RNA-Seq, we identified the HIPPO signaling pathway to be positively regulated by WT KRAS in PDAC cells.
View Article and Find Full Text PDFAndrogen receptor (AR) plays a central role in driving prostate cancer (PCa) progression. How AR promotes this process is still not completely clear. Herein, we used single-cell transcriptome analysis to reconstruct the transcriptional network of AR in PCa.
View Article and Find Full Text PDFAnimal interphase chromosomes are organized into topologically associating domains (TADs). How TADs are formed is not fully understood. Here, we combined high-throughput chromosome conformation capture and gene silencing to obtain insights into TAD dynamics in Xenopus tropicalis embryos.
View Article and Find Full Text PDFWe elucidated the anti-inflammatory mechanisms of IL-38 in allergic asthma. Human bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly (I:C)/LyoVec or infection-related cytokine TNF-α to induce expression of cytokines/chemokines/adhesion molecules. House dust mite (HDM)-induced allergic asthma and humanized allergic asthma NOD/SCID murine models were established to assess anti-inflammatory mechanisms in vivo.
View Article and Find Full Text PDFPyruvate is a key metabolite in glycolysis and the tricarboxylic acid (TCA) cycle. Exogenous pyruvate modulates metabolism, provides cellular protection, and is essential for the maintenance of human preimplantation embryos and human embryonic stem cells (hESCs). However, little is known about how pyruvate contributes to cell-fate determination during epiblast stage.
View Article and Find Full Text PDFThe aberrant activities of transcription factors such as the androgen receptor (AR) underpin prostate cancer development. While the AR -regulation has been extensively studied in prostate cancer, information pertaining to the spatial architecture of the AR transcriptional circuitry remains limited. In this paper, we propose a novel framework to profile long-range chromatin interactions associated with AR and its collaborative transcription factor, erythroblast transformation-specific related gene (ERG), using chromatin interaction analysis by paired-end tag (ChIA-PET).
View Article and Find Full Text PDFEstrogen drives breast cancer (BCa) progression by directly activating estrogen receptor α (ERα). However, because of the stochastic nature of gene transcription, it is important to study the estrogen signaling pathway at the single-cell level to fully understand how ERα regulates transcription. Here, we performed single-cell transcriptome analysis on ERα-positive BCa cells following 17β-estradiol stimulation and reconstructed the dynamic estrogen-responsive transcriptional network from discrete time points into a pseudotemporal continuum.
View Article and Find Full Text PDFObjectives: Drug combination in cancer therapy aims to achieve synergistic therapeutic effect, reduced drug dosage, reduced drug toxicity and minimizes or delays the induction of drug resistance. In the present study, we investigated the anticancer effects of the combination of two metabolic modulators, dichloroacetate (DCA) and bacillus caldovelox arginase (BCA) (or pegyated human arginase (HA)).
Methods: The combination treatments were evaluated in MCF-7 and MDA-MB 231 cells as well as in MDA-MB 231 breast cancer xenograft model.