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Single-cell spatial analysis stratifies lung adenocarcinoma with rare actionable mutations and reveals immune-modulatory cellular crosstalk
Lung adenocarcinoma (LUAD) harboring distinct actionable oncogenic mutations exhibits differential responses to immune checkpoint inhibitors (ICI); however, the underlying mechanisms remain elusive. Here, we report comprehensive single-cell spatial atlases of tumors from 38 LUAD patients, …
Read PDFSingle-Cell RNA-Seq Combined With Bulk RNA-Seq Revealed the Involvement of Pancreatic Cancer Tissue-Resident Macrophages in Tumour Progression and the Immunotherapy Response
Pancreatic cancer remains a highly lethal malignancy with limited therapeutic efficacy and untapped immunotherapeutic potential, largely constrained by immune cell heterogeneity in the tumour microenvironment. Tumour-associated macrophages (TAMs), especially tissue-resident macrophages (TRMs), exert complex regulatory …
Read PDFLessons from single cell omics: admixed American ancestry and sex confer cardiometabolic disease risk in Mexicans
BACKGROUND: Subcutaneous adipose tissue (SAT), the key human fat depot for cardiometabolic health, exhibits high cellular heterogeneity. However, the contributions of contexts and cardiometabolic diseases (CMDs) to this heterogeneity are poorly understood, especially in admixed …
Read PDFEvaluating single-cell ATAC-seq atlasing technologies using sequence-to-function modeling
Deciphering the cis-regulatory logic underlying cell type identity remains a key challenge in biology. Single-cell chromatin accessibility (scATAC-seq) atlases enable training of sequence-to-function (S2F) deep learning models to decode enhancer logic. Yet, optimal criteria for …
Read PDFSingle cell profiling framework reveals metabolic subpopulations as drivers of bioproduction heterogeneity
Heterogeneity within clonal cell populations remains a critical bottleneck within bioprocess engineering, notably by undermining bioproduction yields. Efforts to mitigate its impact have, however, been hampered by technological difficulties quantifying metabolism at the single-cell level. …
Read PDFPooled single-cell screen in colorectal cancer defines transcriptional modules linked to oncogenes
Oncogenic mutations shape colorectal cancer (CRC) biology, yet their impact on transcriptional phenotypes remains incompletely understood, and their individual prognostic value is limited. Here, we perform a pooled single-cell transcriptomic screen of over 100,000 CRC …
Read PDFMacrophage-Mediated Cellular Communication Networks in Lung Squamous Cell Carcinoma and Adenocarcinoma Revealed by Single-Cell Sequencing
<h4>Background</h4>Lung cancer, particularly the non-small cell lung cancer (NSCLC) subtypes lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), exhibits high heterogeneity and high mortality. This study aimed to explore their tumor microenvironment (TME) features, …
Read PDFSingle-Cell Lineage Tracing Uncovers Resistance Signatures and Sensitizing Strategies to FLT3 Inhibitors in Acute Myeloid Leukemia
Whereas FMS-like tyrosine kinase-3 (FLT3) inhibitors have significantly improved the treatment of aggressive FLT3-mutated acute myeloid leukemia (AML), the emergence of resistance remains as a major challenge. In this study, we applied our recently developed …
Read PDFSingle-cell sequencing in molecular diagnostics: Transformative yet untapped potential
Single-cell sequencing (SCS) techniques have the potential to offer precise insights into cellular diversity by revealing unique genetic and transcriptomic profiles at the single-cell level. This advanced technology has been used extensively in research, but …
Read PDFA novel single-cell level evaluation method for corneal endothelial cell function
Approximately 10 million people worldwide suffer from corneal diseases, with endothelial dysfunction being a leading cause of blindness. Current morphological assessments lack sensitivity for detecting early corneal endothelial abnormalities. Here, we present a novel diagnostic …
Read PDFSingle-cell analysis reveals the prognostic role of immune escape in the colorectal cancer microenvironment
<h4>Background</h4>Colorectal cancer (CRC) is a malignant disease that poses a significant threat to human health; however, early diagnostic and treatment strategies for it remain limited. Immune evasion is a critical factor contributing to treatment failure …
Read PDFSingle-cell analyses identify independent aging processes that compete to determine cellular fate in budding yeast
Phenotypic heterogeneity is prevalent during aging, yet its underlying molecular drivers remain poorly understood. In budding yeast, two distinct aging trajectories, characterized by either ribosomal DNA (rDNA) instability or mitochondrial decline, have been proposed to …
Read PDFSingle cell Raman spectroscopic profiles predict treatment responses in patients with <i>de novo</i> acute myeloid leukemia
<h4>Introduction</h4>Leukemia is a clonal malignant proliferative disease originating from hematopoietic stem cells. Although its treatment strategy has gradually developed from traditional chemotherapy to a multimodal treatment system including novel targeted therapy and immunotherapy, primary drug …
Read PDFSingle-cell transcriptomics reveal mechanisms of skeletal muscle differentiation across duck embryonic development
Skeletal muscle development is cornerstone of vertebrate locomotion, relies on the functionally distinct muscle fiber-type. Although the cellular dynamics in myogenesis have been extensively studied, the developmental origins and pathways governing fiber-type diversification remain unresolved. …
Read PDFSuggested experimental design and computational modeling to infer single-cell lipid dynamics from a single destructive measurement
Cellular heterogeneity is a fundamental facet of cell biology, influencing cellular signaling, metabolism, and gene regulation. Its accurate quantification requires measurements at the single-cell level. Most high-throughput single-cell technologies provide only a snapshot of cellular …
Read PDFA single-cell multi-omics assay for simultaneous measurement of vector copy number and protein expression in CAR T cells
Chimeric antigen receptor T cell (CAR T) immunotherapies have transformed cancer treatment. These therapies typically involve lentiviral vector-mediated CAR gene integration, followed by reinfusion into patients, necessitating rigorous quality control. Critical parameters, including transduction efficiency …
Read PDFToward single-cell control: noise-robust perfect adaptation in biomolecular systems
Robust perfect adaptation (RPA), whereby a consistent output level is maintained even after a disturbance, is a highly desired feature in biological systems. This property can be achieved at the population average level by combining …
Read PDFIntegrative Multiomics and Single-Cell Profiling Identify TNFRSF1A<sup>+</sup> Macrophages as a Prognostic and Therapeutic Target in Diffuse Large B-cell Lymphoma
The tumor microenvironment plays a critical role in therapeutic resistance in diffuse large B-cell lymphoma (DLBCL), yet actionable targets within the immune cells remain largely undefined. Through integrative multiomics profiling, we identified tumor necrosis factor …
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