Synthetic biology efforts have also led to the development of photosynthetic cyanobacteria as"autotrophic cell factories"for biosynthesis of various biofuels directly from CO_(2).However,the low tolerance to...Synthetic biology efforts have also led to the development of photosynthetic cyanobacteria as"autotrophic cell factories"for biosynthesis of various biofuels directly from CO_(2).However,the low tolerance to toxicity of biofuels has restricted the economic application of cyanobacterial hosts.In this study,RNAseq transcriptomics was employed to reveal stress responses to exogenous n-hexane in Synechocystis sp.PCC 6803.Functional enrichment analysis of the transcriptomic data showed that signal transduction systems were induced significantly.To further identify regulatory genes related to n-hexane tolerance,a library of transcriptional regulators(TRs)deletion mutants was then screened for their roles in nhexane tolerance.The results showed that a knockout mutant of slr0724 that encodes an Hta R suppressor protein was more tolerant to n-hexane than the wild type,indicating the involvement of slr0724 in nhexane tolerance.This study provides the foundation for better understanding the cellular responses to n-hexane in Synechocystis sp.PCC 6803,which could contribute to the further engineering of nhexane tolerance in cyanobacteria.展开更多
Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual ...Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual curation,which is cumbersome and subjective.The increasing number of scRNA-seq datasets,as well as numerous published genetic studies,has motivated us to build a comprehensive human cell type reference atlas.Here,we present decoding Cell type Specificity(deCS),an automatic cell type annotation method augmented by a comprehensive collection of human cell type expression profiles and marker genes.We used deCS to annotate scRNAseq data from various tissue types and systematically evaluated the annotation accuracy under different conditions,including reference panels,sequencing depth,and feature selection strategies.Our results demonstrate that expanding the references is critical for improving annotation accuracy.Compared to many existing state-of-the-art annotation tools,deCS significantly reduced computation time and increased accuracy.deCS can be integrated into the standard scRNA-seq analytical pipeline to enhance cell type annotation.Finally,we demonstrated the broad utility of deCS to identify trait-cell type associations in 51 human complex traits,providing deep insights into the cellular mechanisms underlying disease pathogenesis.展开更多
Understanding the molecular mechanisms of coronavirus disease 2019(COVID-19)pathogenesis and immune response is vital for developing therapies.Single-cell RNA sequencing has been applied to delineate the cellular hete...Understanding the molecular mechanisms of coronavirus disease 2019(COVID-19)pathogenesis and immune response is vital for developing therapies.Single-cell RNA sequencing has been applied to delineate the cellular heterogeneity of the host response toward COVID-19 in multiple tissues and organs.Here,we review the applications and findings from over 80 original COVID-19 single-cell RNA sequencing studies as well as many secondary analysis studies.We describe that single-cell RNA sequencing reveals multiple features of COVID-19 patients with different severity,including cell populations with proportional alteration,COVID-19-induced genes and pathways,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in single cells,and adaptation of immune repertoire.We also collect published single-cell RNA sequencing datasets from original studies.Finally,we discuss the limitations in current studies and perspectives for future advance.展开更多
基金supported by grants from the National Key Research and Development Program of China(2020YFA0906800,2021YFA0909700,2018YFA0903600 and 2019YFA0904600)。
文摘Synthetic biology efforts have also led to the development of photosynthetic cyanobacteria as"autotrophic cell factories"for biosynthesis of various biofuels directly from CO_(2).However,the low tolerance to toxicity of biofuels has restricted the economic application of cyanobacterial hosts.In this study,RNAseq transcriptomics was employed to reveal stress responses to exogenous n-hexane in Synechocystis sp.PCC 6803.Functional enrichment analysis of the transcriptomic data showed that signal transduction systems were induced significantly.To further identify regulatory genes related to n-hexane tolerance,a library of transcriptional regulators(TRs)deletion mutants was then screened for their roles in nhexane tolerance.The results showed that a knockout mutant of slr0724 that encodes an Hta R suppressor protein was more tolerant to n-hexane than the wild type,indicating the involvement of slr0724 in nhexane tolerance.This study provides the foundation for better understanding the cellular responses to n-hexane in Synechocystis sp.PCC 6803,which could contribute to the further engineering of nhexane tolerance in cyanobacteria.
基金supported by National Institutes of Health grants(Grant Nos.R01LM012806R,I01DE030122,and R01DE029818)support from Cancer Prevention and Research Institute of Texas(Grant Nos.CPRIT RP180734 and RP210045),United States.
文摘Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual curation,which is cumbersome and subjective.The increasing number of scRNA-seq datasets,as well as numerous published genetic studies,has motivated us to build a comprehensive human cell type reference atlas.Here,we present decoding Cell type Specificity(deCS),an automatic cell type annotation method augmented by a comprehensive collection of human cell type expression profiles and marker genes.We used deCS to annotate scRNAseq data from various tissue types and systematically evaluated the annotation accuracy under different conditions,including reference panels,sequencing depth,and feature selection strategies.Our results demonstrate that expanding the references is critical for improving annotation accuracy.Compared to many existing state-of-the-art annotation tools,deCS significantly reduced computation time and increased accuracy.deCS can be integrated into the standard scRNA-seq analytical pipeline to enhance cell type annotation.Finally,we demonstrated the broad utility of deCS to identify trait-cell type associations in 51 human complex traits,providing deep insights into the cellular mechanisms underlying disease pathogenesis.
基金supported by National Institutes of Health grants(R01LM012806,R01DE030122,and R01DE029818)Cancer Prevention and Research Institute of Texas(CPRIT RP180734 and RP210045)The funders had no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript.Funding for open access charge:CPRIT(RP180734)。
文摘Understanding the molecular mechanisms of coronavirus disease 2019(COVID-19)pathogenesis and immune response is vital for developing therapies.Single-cell RNA sequencing has been applied to delineate the cellular heterogeneity of the host response toward COVID-19 in multiple tissues and organs.Here,we review the applications and findings from over 80 original COVID-19 single-cell RNA sequencing studies as well as many secondary analysis studies.We describe that single-cell RNA sequencing reveals multiple features of COVID-19 patients with different severity,including cell populations with proportional alteration,COVID-19-induced genes and pathways,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in single cells,and adaptation of immune repertoire.We also collect published single-cell RNA sequencing datasets from original studies.Finally,we discuss the limitations in current studies and perspectives for future advance.