Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by abnormal cellular and humoral immune responses and excessive autoantibody production.The precise pathologic mechanism of SLE remains e...Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by abnormal cellular and humoral immune responses and excessive autoantibody production.The precise pathologic mechanism of SLE remains elusive.The advent of single-cell RNA sequencing(scRNA-seq)enables unbiased analysis of the molecular differences of cell populations at the single-cell level.We used scRNA-seq to profile the transcriptomes of peripheral blood mononuclear cells from an SLE patient compared with a healthy control(HC).A total of 16,021 cells were analyzed and partitioned into 12 distinct clusters.The marker genes of each cluster and the four major immune cell types(B cells,CD4+T cells,CD8+T cells,myeloid cells,and NK cells)were determined.Moreover,several genes involved in antigen processing and presentation through MHCII were highly enriched.GO enrichment analyses revealed abnormal gene expression patterns and signaling pathways in SLE.Of note,pseudotime analysis revealed that there was a different lineage hierarchy in the peripheral blood mononuclear cells(PBMCs)of the SLE patient,indicating that the cell states were substantially altered under disease conditions.Our analysis provides a comprehensive map of the cell types and states of the PBMCs of SLE patients at the single-cell level for a better understanding of the pathogenesis,diagnosis,and treatment of SLE.展开更多
Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and function.The natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflamm...Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and function.The natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or dysfunction.In this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels.Our results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer cells.These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.展开更多
Diabetic nephropathy(DN)has become the leading cause of end-stage renal disease with high morbidity and mortality among individuals with diabetes mellitus.Although functional alterations of renal infiltrating immune c...Diabetic nephropathy(DN)has become the leading cause of end-stage renal disease with high morbidity and mortality among individuals with diabetes mellitus.Although functional alterations of renal infiltrating immune cells have been reported as part of the pathological mechanism of DN,the understanding of the immune response underlying peripheral blood mononuclear cells(PBMCs)in DN remains limited.Here,single-cell RNA sequencing(scRNA-seq)was used toprofile the transcriptomic signatures of PBMCs from DN patients.展开更多
基金the National Natural Science Foundation of China(Grant No.81671596)the Natural Science Foundation of Guangxi(Grant No.2019GXNSFBA245032,and No.2017GXNSFAA198375)+6 种基金the Guangxi Science and Technology Plan Project(Gui Ke AD20238021)the National Science Foundation for Young Scientists of China(Grant No.31700795)the science and technology plan of Shenzhen(No.JCYJ20170307095606266)Shenzhen science and technology research foundation(JCYJ20160422154407256)Sanming project of medicine in Shenzhen,the group of Rheumatology and Immunology led by Xiaofeng Zeng of Peking Union medical college Hospital and Dongzhou Liu in Shenzhen People’s Hospital(SYJY201704 and SYJY201705)the open funds of the Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation(2019KF004)Guilin science research and technology development project(20190218-5-5).
文摘Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by abnormal cellular and humoral immune responses and excessive autoantibody production.The precise pathologic mechanism of SLE remains elusive.The advent of single-cell RNA sequencing(scRNA-seq)enables unbiased analysis of the molecular differences of cell populations at the single-cell level.We used scRNA-seq to profile the transcriptomes of peripheral blood mononuclear cells from an SLE patient compared with a healthy control(HC).A total of 16,021 cells were analyzed and partitioned into 12 distinct clusters.The marker genes of each cluster and the four major immune cell types(B cells,CD4+T cells,CD8+T cells,myeloid cells,and NK cells)were determined.Moreover,several genes involved in antigen processing and presentation through MHCII were highly enriched.GO enrichment analyses revealed abnormal gene expression patterns and signaling pathways in SLE.Of note,pseudotime analysis revealed that there was a different lineage hierarchy in the peripheral blood mononuclear cells(PBMCs)of the SLE patient,indicating that the cell states were substantially altered under disease conditions.Our analysis provides a comprehensive map of the cell types and states of the PBMCs of SLE patients at the single-cell level for a better understanding of the pathogenesis,diagnosis,and treatment of SLE.
基金This work was supported by the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(2020YFE0205100,China)National Key Research and Development Program of China(grant number 2020YFA0908000,2022YFC2303600)+6 种基金the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(grant number ZYYCXTD-C-202002,China)the National Natural Science Foundation of China(grant number 82074098,81841001),the Fundamental Research Funds for the Central Public Welfare Research Institutes(grant number ZZ16-ND-10-23,ZZ15-ND-10,ZZ14-ND-010,ZZ14-FL-002,ZZ14-YQ-050,ZZ14-YQ-051,China)Shenzhen Science and Technology Innovation Commission(grant number JCYJ20210324115800001 and JCYJ20210324114014039,China)the Shenzhen Medical Research Fund(B2302051,China)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(CW202002,China)CACMS Innovation Fund(CI2023E002,CI2021A05101 and CI2021A05104,China)support from State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs,Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2023D003,CI2021B014,China).
文摘Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and function.The natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or dysfunction.In this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels.Our results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer cells.These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.
基金supported by the Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(China)(No.SZGSP001)Shenzhen Governmental Sustainable Development Fund(Guangdong,China)(No.KCXFZ20201221173612034)+3 种基金the National Natural Science Foundation of China(China)(No.82170842)the Natural ScienceFoundation of Shenzhen City(China)(No.KCXFZ20201221173600001)Guangdong Basic and Applied Basic Research Foundation(China)(No.2021A1515012164)Shenzhen Key Laboratory of Kidney Diseases(No.ZDSYS20150430161-6234)。
文摘Diabetic nephropathy(DN)has become the leading cause of end-stage renal disease with high morbidity and mortality among individuals with diabetes mellitus.Although functional alterations of renal infiltrating immune cells have been reported as part of the pathological mechanism of DN,the understanding of the immune response underlying peripheral blood mononuclear cells(PBMCs)in DN remains limited.Here,single-cell RNA sequencing(scRNA-seq)was used toprofile the transcriptomic signatures of PBMCs from DN patients.