Bronchoalveolar Lavage Single-Cell Transcriptomics Identifies Immune Cells Driving COVID-19 Severity in Patients DOI Creative Commons
Njinju Asaba Clinton,

Razieh Bitazar,

Patrick Ndonyi Labonté

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 23, 2024

The continuous threats posed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, including emergence of potentially more infectious and deadly variants, necessitate ongoing studies to uncover novel detailed mechanisms driving disease severity. Using single-cell transcriptomics, we conducted a secondary data analysis bronchoalveolar lavage fluid (BALF) from COVID-19 patients varying severities healthy controls comprehensively examine immune responses. We observed significant cell alterations correlating with In severe cases, macrophages showed upregulation pro-inflammatory genes TNFα IL1β, contributing inflammation tissue damage. Neutrophils exhibited increased activation, marked S100A8, CXCL8, IL1β expression, extended viability reduced phagocytosis. Genes such as MCL1 HIF1α supported viability, while MSR1 MRC1 indicated Enhanced formation neutrophil extracellular traps (NETs) clearance, NET-associated markers, were linked thrombo-inflammation organ Both neutrophils in cases impaired efferocytosis, decreased expression TREM2 downregulation FCGR3B neutrophils, leading accumulation apoptotic cells exacerbating inflammation. characterized M1 high milder had M2 elevated PPARγ. Low-density (LDNs) significantly showing higher CXCR4 CD274 lower compared high-density (HDNs). NK T demonstrated altered receptor gene activation markers IFNγ ISG15, suggesting paradoxical state exhaustion. This imbalance suggests potential mechanism for dysregulation ineffective antiviral responses COVID-19. highlights critical role dysregulated neutrophil, macrophage, NK, identifying therapeutic targets providing insights into disease.

Language: Английский

Integrated cancer cell-specific single-cell RNA-seq datasets of immune checkpoint blockade-treated patients DOI Creative Commons
Mahnoor Gondal, Marcin Cieślik, Arul M. Chinnaiyan

et al.

Scientific Data, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 22, 2025

Abstract Immune checkpoint blockade (ICB) therapies have emerged as a promising avenue for the treatment of various cancers. Despite their success, efficacy these treatments is variable across patients and cancer types. Numerous single-cell RNA-sequencing (scRNA-seq) studies been conducted to unravel cell-specific responses ICB treatment. However, are limited in sample sizes require advanced coding skills exploration. Here, we compiled eight scRNA-seq datasets from nine types, encompassing 223 patients, 90,270 cells, 265,671 other cell This compilation forms unique resource tailored investigate how cells respond We meticulously curated, quality-checked, pre-processed, analyzed data, ensuring easy access researchers. Moreover, designed user-friendly interface seamless By sharing code data creating interfaces, aim assist fellow These resources offer valuable support those interested leveraging exploring diverse facilitating comprehensive understanding responses.

Language: Английский

Citations

2

Identification of cancer cell-intrinsic biomarkers associated with tumor progression and characterization of SFTA3 as a tumor suppressor in lung adenocarcinomas DOI Creative Commons
Yu Zhao, Chengcheng Zhou, Ling Zuo

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 8, 2025

Recent advancements in contemporary therapeutic approaches have increased the survival rates of lung cancer patients; however, long-term benefits remain constrained, underscoring pressing need for novel biomarkers. Surfactant-associated 3 (SFTA3), a long non-coding RNA predominantly expressed normal epithelial cells, plays crucial role development. Nevertheless, its function adenocarcinoma (LUAD) remains inadequately understood. Single-cell sequencing data were utilized to identify cell-intrinsic gene signatures associated with progression LUAD, and their roles LUAD comprehensively analyzed. Serum samples collected quantify expression levels SFTA3 patients. Furthermore, series biological experiments, including cell viability assays, scratch wound healing colony formation conducted demonstrate tumor-suppressive effects SFTA3. was performed elucidate molecular mechanisms underlying cells. We constructed prognostic model comprising eight genes: ALDOA, ATP5MD, SERPINH1, SFTA3, SLK, U2SURP, SCGB1A1, SCGB1A3. The effectively stratified patients into high- low-risk categories, revealing that experienced superior clinical outcomes, exhibited an immunologically hot tumor microenvironment (TME), had greater probability responding immunotherapy. In contrast, high-risk group cold TME may benefit more from chemotherapy. our study revealed progressive decrease cells correlated advancement. Notably, serum significantly decreased suggesting potential utility liquid biopsy diagnosis. Additionally, knockdown enhances proliferation migration whereas overexpression inhibits these phenotypes. epithelial-mesenchymal transition pathway enriched following silencing, impact by modulating this process. also identified key transcription factors epigenetic implicated downregulation LUAD. developed robust as biomarker applications diagnosis, prognosis, personalized treatment findings offer new insights tumorigenesis immune evasion.

Language: Английский

Citations

0

Bronchoalveolar lavage single-cell transcriptomics reveals immune dysregulations driving COVID-19 severity DOI Creative Commons
Njinju Asaba Clinton,

Razieh Bitazar,

Patrick Labonté

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0309880 - e0309880

Published: Feb. 10, 2025

The continuous threats posed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, including emergence of potentially more infectious and deadly variants, necessitate ongoing studies to uncover novel detailed mechanisms driving disease severity. Using single-cell transcriptomics, we conducted a secondary data analysis bronchoalveolar lavage fluid (BALF) from COVID-19 patients varying severities healthy controls comprehensively examine immune responses. We observed significant cell alterations correlating with In severe cases, macrophages showed upregulation pro-inflammatory genes TNFα IL1β, contributing inflammation tissue damage. Neutrophils exhibited increased activation, marked S100A8, CXCL8, IL1β expression, extended viability reduced phagocytosis. Genes such as MCL1 HIF1α supported viability, while MSR1 MRC1 indicated Enhanced formation neutrophil extracellular traps (NETs) clearance, NET-associated markers, were linked thrombo-inflammation organ Both neutrophils in cases impaired efferocytosis, decreased expression TREM2 downregulation FCGR3B neutrophils, leading accumulation apoptotic cells exacerbating inflammation. characterized M1 high milder had M2 elevated PPARγ. Dendritic (DCs) proportions attenuated MHC class I (HLA-A, HLA-B, HLA-C) co-stimulatory molecules (CD80, CD86), alongside cytochrome c indicating antigen presentation enhanced apoptosis. NK T demonstrated altered receptor gene activation markers IFNγ ISG15, suggesting paradoxical state exhaustion. This highlights critical role dysregulated neutrophil, macrophage, dendritic cell, NK, responses identifying potential therapeutic targets providing insights into disease.

Language: Английский

Citations

0

Single-Cell Transcriptomic Approaches for Decoding Non-Coding RNA Mechanisms in Colorectal Cancer DOI Creative Commons
Mahnoor Gondal, Hafiz Muhammad Umer Farooqi

Non-Coding RNA, Journal Year: 2025, Volume and Issue: 11(2), P. 24 - 24

Published: March 10, 2025

Non-coding RNAs (ncRNAs) play crucial roles in colorectal cancer (CRC) development and progression. Recent developments single-cell transcriptome profiling methods have revealed surprising levels of expression variability among seemingly homogeneous cells, suggesting the existence many more cell types than previously estimated. This review synthesizes recent advances ncRNA research CRC, emphasizing bioinformatics approaches for their analysis. We explore computational tools used identification, characterization, functional prediction with a focus on RNA sequencing (scRNA-seq) data. The highlights key strategies, including sequence-based structure-based approaches, machine learning applications, multi-omics data integration. discuss how these techniques can be applied to analyze differential expression, perform enrichment, construct regulatory networks involving ncRNAs CRC. Additionally, we examine role leveraging as diagnostic prognostic biomarkers also scRNA-seq studies revealing heterogeneity aims provide comprehensive overview current state CRC outline future directions this rapidly evolving field, integration experimental validation advance our understanding biology

Language: Английский

Citations

0

RNA-based diagnostic innovations: A new frontier in diabetes diagnosis and management DOI Creative Commons
Esther Ugo Alum,

Ernest Nnamdi Ikpozu,

Christian Emeka Offor

et al.

Diabetes and Vascular Disease Research, Journal Year: 2025, Volume and Issue: 22(2)

Published: March 1, 2025

Background/Objective: Diabetes mellitus (DM) remains a major global health challenge due to its chronic nature and associated complications. Traditional diagnostic approaches, though effective, often lack the sensitivity required for early-stage detection. Recent advancements in molecular biology have identified RNA molecules, particularly non-coding RNAs such as microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), promising biomarkers diabetes. This review aims explore role of RNA-based diagnosis, prognosis, management diabetes, highlighting their potential revolutionize diabetes care. Method: A comprehensive literature was conducted using electronic databases including PubMed, Scopus, Web Science. Articles published up 2024 were screened analyzed extract relevant findings related diagnostics Emphasis placed on studies demonstrating clinical utility, mechanistic insights, translational molecules. Results: Numerous species, miRNAs miR-375, miR-29, lncRNAs like H19 MEG3, exhibit altered expression patterns diabetic patients. These molecules are involved key regulatory pathways glucose metabolism, insulin resistance, β-cell function. Circulating detectable various biofluids, enabling non-invasive approaches. Emerging technologies, sequencing liquid biopsy platforms, enhanced specificity detection, fostering development novel tools personalized therapeutic strategies. Conclusion: hold significant promise advancing early risk stratification, monitoring Despite current challenges standardization validation, integration into routine practice could transform management, paving way precision medicine Further research multi-center trials essential validate these facilitate approval implementation.

Language: Английский

Citations

0

Bronchoalveolar Lavage Single-Cell Transcriptomics Identifies Immune Cells Driving COVID-19 Severity in Patients DOI Creative Commons
Njinju Asaba Clinton,

Razieh Bitazar,

Patrick Ndonyi Labonté

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 23, 2024

The continuous threats posed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, including emergence of potentially more infectious and deadly variants, necessitate ongoing studies to uncover novel detailed mechanisms driving disease severity. Using single-cell transcriptomics, we conducted a secondary data analysis bronchoalveolar lavage fluid (BALF) from COVID-19 patients varying severities healthy controls comprehensively examine immune responses. We observed significant cell alterations correlating with In severe cases, macrophages showed upregulation pro-inflammatory genes TNFα IL1β, contributing inflammation tissue damage. Neutrophils exhibited increased activation, marked S100A8, CXCL8, IL1β expression, extended viability reduced phagocytosis. Genes such as MCL1 HIF1α supported viability, while MSR1 MRC1 indicated Enhanced formation neutrophil extracellular traps (NETs) clearance, NET-associated markers, were linked thrombo-inflammation organ Both neutrophils in cases impaired efferocytosis, decreased expression TREM2 downregulation FCGR3B neutrophils, leading accumulation apoptotic cells exacerbating inflammation. characterized M1 high milder had M2 elevated PPARγ. Low-density (LDNs) significantly showing higher CXCR4 CD274 lower compared high-density (HDNs). NK T demonstrated altered receptor gene activation markers IFNγ ISG15, suggesting paradoxical state exhaustion. This imbalance suggests potential mechanism for dysregulation ineffective antiviral responses COVID-19. highlights critical role dysregulated neutrophil, macrophage, NK, identifying therapeutic targets providing insights into disease.

Language: Английский

Citations

0