Single-Cell RNA Sequencing in Unraveling Acquired Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: New Perspectives

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1483 - 1483

Опубликована: Фев. 11, 2025

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated remarkable efficacy in treating non-small cell lung cancer (NSCLC), but acquired resistance greatly reduces and poses a significant challenge to patients. While numerous studies investigated the mechanisms underlying EGFR-TKI resistance, its complexity diversity make existing understanding still incomplete. Traditional approaches frequently struggle adequately reveal process of drug development through mean value analysis at overall cellular level. In recent years, rapid single-cell RNA sequencing technology has introduced transformative method for analyzing gene expression changes within tumor cells resolution. It not only deepens our microenvironment heterogeneity associated with also identifies potential biomarkers resistance. this review, we highlight critical role research, particular focus on application exploring EGFR-TKI-acquired NSCLC. We emphasize elucidating mechanism promise informing more precise personalized treatment strategies. Ultimately, approach aims advance NSCLC toward new era precision medicine.

Язык: Английский

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Plate-based long-read single cell gene- and isoform transcriptome profiling using scLIS-seq

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

While contemporary short-read single cell RNA-sequencing allows to decipher tissue composition, discrimination between transcript isoforms remains challenging. Here, we propose long-read isoform sequencing (scLIS-seq), and highlight its performance on Jurkat HEK293T cells in direct comparison Smart-seq3xpress (SS3X). scLIS-seq demonstrates sensitive gene detection with high correlation compared SS3X detects at least 10 of over 2600 genes, while 17.1–21.6% the reads supported novel isoforms. Direct SS3X-reconstructed demonstrated scLIS-seq’s superiority. Overall, provides a powerful scRNA-seq strategy, enabling transcriptome analysis detection.

Язык: Английский

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The hidden connection between gut microbiota and periprosthetic joint infections: a scoping review

Journal of Bone and Joint Infection, Год журнала: 2025, Номер 10(2), С. 85 - 92

Опубликована: Март 28, 2025

Abstract. Background: Periprosthetic joint infections (PJIs) pose a significant challenge in orthopedic surgery, and emerging evidence suggests that the gut microbiome may play crucial role their development management. Despite rarity of these infections, continuous increase prosthetic arthroplasties has made understanding how to prevent them more pressing. A stronger comprehension disruption this can lead other pre-surgical risks be preventing them. Objective: This article aims provide topic through analysis different pieces already existing literature help draw new conclusions raise potential questions need answering. Methods: comprehensive search strategy without filters was employed, multiple papers were thoroughly analyzed, understood, compiled into paper. Conclusions: limitations some analyzed studies finite evidence, paper there could connection between periprosthetic compromised microbiome. However, further research is required definitive conclusion.

Язык: Английский

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Challenges and Progress in RNA Velocity: Comparative Analysis Across Multiple Biological Contexts

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 29, 2024

Abstract Single-cell RNA sequencing is revolutionizing our understanding of cell state dynamics, allowing researchers to observe the progression individual cells’ transcriptomic profiles over time. Among computational techniques used predict future cellular states, velocity has emerged as a predominant tool for modeling transcriptional dynamics. leverages mRNA maturation process generate vectors that likely cell, offering insights into differentiation, aging, and disease progression. Although this technique shown promise across biological fields, performance accuracy varies depending on method dataset. We established comparative pipeline analyzed five methods three datasets based local consistency, agreement, identification driver genes, robustness depth. This benchmark provides resource scientists understand strengths limitations different methods.

Язык: Английский

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Single-cell Rapid Capture Hybridization sequencing (scRaCH-seq) to reliably detect isoform usage and coding mutations in targeted genes at a single-cell level

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 30, 2024

Abstract Single-cell long-read sequencing has transformed our understanding of isoform usage and the mutation heterogeneity between cells. Despite unbiased in-depth analysis, low throughput often results in insufficient read coverage thereby limiting ability to perform calling for specific genes. Here, we developed a s ingle- c ell Ra pid Capture H ybridization seq uencing (scRaCH-seq) method that demonstrated high specificity efficiency capturing targeted transcripts using sequencing, allowing an analysis status transcript genes interest. The includes creating probe panel capture, barcoded primers pooling efficient via Oxford Nanopore Technologies platforms. scRaCH-seq is applicable stored indexed single-cell cDNA which allows be combined with existing short-read RNA-seq datasets. In investigation BTK SF3B1 samples from patients chronic lymphocytic leukaemia (CLL), detected isoforms mutations sensitivity. Integration scRNA-seq data revealed significant gene expression differences SF3B1-mutated CLL cells, though it did not impact sensitivity anti-cancer drug venetoclax. scRaCH-seq’s capability study multiple makes powerful tool genomics.

Язык: Английский

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RPS24 alternative splicing is a marker of cancer progression and epithelial-mesenchymal transition

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 10, 2024

Abstract Although alternative splicing (AS) is a major mechanism that adds diversity to gene expression patterns, its precise role in generating variability ribosomal proteins, known as heterogeneity, remains unclear. The protein S24 ( RPS24 ) gene, encoding component, undergoes AS; however, in-depth studies have been challenging because of three microexons between exons 4 and 6. We conducted detailed analysis AS isoforms using direct approach investigate the junctions related these microexons, focusing on four isoforms. Each showed tissue specificity relative differences among cancer types. Significant proportions cancerous normal tissues across diverse types were also observed. Our study highlighted significant correlation levels specific isoform epithelial–mesenchymal transition process lung breast cancers. research contributes better understanding intricate regulatory mechanisms governing genes highlights biological implications development tumorigenesis.

Язык: Английский

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Long-read sequencing for brain tumors

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Июнь 10, 2024

Brain tumors and genomics have a long-standing history given that glioblastoma was the first cancer studied by genome atlas. The numerous continuous advances through decades in sequencing technologies aided advanced molecular characterization of brain for diagnosis, prognosis, treatment. Since implementation biomarkers WHO CNS 2016, has been integrated into diagnostic criteria. Long-read sequencing, also known as third generation is an emerging technique allows longer DNA segments leading to improved detection structural variants epigenetics. These capabilities are opening way better tumors. Here, we present comprehensive summary state art third-generation application tumor We discuss advantages potential new implementations long-read clinical paradigms neuro-oncology patients.

Язык: Английский

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Data-guided direct reprogramming of human fibroblasts into the hematopoietic lineage

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 26, 2024

Abstract Direct reprogramming of human fibroblasts into hematopoietic stem cells (HSCs) shows promise for generating autologous treatment blood and immune-related diseases. However, low conversion efficiency existing protocols points to gaps in our understanding opportunities identification optimal transcription factor (TF) combinations, which is a major bottleneck HSC generation. In this study, we tested novel algorithmically-predicted TF recipe (GATA2, GFIB1, FOS, REL, STAT5A) inducing HSC-like states. Our induced CD34 + surface expression single-cell transcriptomic signatures similar those native HSCs. Transcriptional heterogeneity within reprogrammed included differences endothelial-associated genes alternatively spliced transcripts as measured by long- read RNA-sequencing. Further, proposed an approach quantify the relative position spectrum initial target cell This study lays foundation efficient optimization direct protocols.

Язык: Английский

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Roles of prion proteins in mammalian development

Animal Cells and Systems, Год журнала: 2024, Номер 28(1), С. 551 - 566

Опубликована: Дек. 10, 2024

Prion protein (PrP) is highly conserved and expressed in most tissues a developmental stage-specific manner. Glycosylated cellular prion (PrP

Язык: Английский

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The Potential Role of Gut Bacteriome Dysbiosis as a Leading Cause of Periprosthetic Infection: A Comprehensive Literature Review

Microorganisms, Год журнала: 2023, Номер 11(7), С. 1778 - 1778

Опубликована: Июль 9, 2023

(1) Background: Periprosthetic joint infections (PJIs) represent a small yet important risk when undertaking arthroplasty; they occur in approximately 1–2% of treatments. These create medical and financial burden for patients healthcare systems. Despite the introduction recognized best clinical practices during arthroplasty operations, it is not possible to further reduce infection after surgery. The purpose this review raise awareness potential role gut dysbiosis development PJIs highlight bacteriome as target preventing them. (2) Methods: We compiled all available data from five databases, examining effects human murine studies, following PRISMA guidelines, total reviewed studies. (3) Results: One one study found Trojan horse theory applicable. Additionally, inflammatory bowel diseases, permeability, oral antibiotic ingestion appeared play promoting cause PJIs, according other three (4) Conclusions: Gut linked an increased PJI.

Язык: Английский

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