Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and ...Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa(CRPC).Methods:We performed single-cell RNA sequencing(scRNA-seq)on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues,two untreated primary PCa tissues,and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa.We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.Results:scRNA-seq profiles revealed substantial inter-and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors.In the malignant epithelial reservoir,cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors,and distinct transcriptional reprogramming processes were activated,highlighting anti-androgen therapy-induced lineage plasticity.Based on the specifically expressed markers of the epithelial subpopulations,we conducted unsupervised clustering analysis in The Cancer Genome Atlas prostate adenocarcinoma(TCGA-PRAD)cohort and identified three molecularly and clinically distinct subtypes.The C1 subtype,characterized by high enrichment of CRPC-enriched epithelial cells,had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments,such as integrin A3(ITGA3)+integrin B1(ITGB1)inhibition.The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy.The C3 subtype had a favorable prognosis.Conclusions:Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME,and our trichotomic molecular taxonomy could help facilitate precision oncology.展开更多
The Odorrana schmackeri sensu la to is a group of cascade frogs that are widely distributed in southern China.However,their taxonomy has long been unresolved and several cryptic species have been reported in the past ...The Odorrana schmackeri sensu la to is a group of cascade frogs that are widely distributed in southern China.However,their taxonomy has long been unresolved and several cryptic species have been reported in the past decade.Previous analyses revealed the existence of three sympatrie species(i.c,O.schmackeri,O.hejiangensis and O.sp2) at the type locality of O.schmackeri(Gaojiayan Town,Yichang City,Hubei Province,China).However,the lack of an original description for the holotype specimen(SMF6241) of O.schmackeri poses a confusing and controversial problem in species nomination within this group.Here,we reevaluate the taxonomic affinities of SMF6241 and examine the distinctness of O.sp2 based on specimens from the type locality.We use integrative approaches that combine morphology with 10 microsatellite loci and bioacoustics.Canonical discriminant analysis of morphological characteristics revealed three distinct groupings(i.e.,O.schmackeri,O.hejiangensis and O.sp2) and attributed SMF6241 to O.schmackeri.Genetic clustering analysis of nuclear DNA also identified three corresponding clusters.In addition,analysis of interspecific variation in morphometrics and acoustics showed divergence between O.sp2 and its sympatric congeners.All lines of evidence from morphological,molecular and bioacoustic approaches suggest the species status of O.sp2,namely Odorrana ichangensis Chen,sp.nov.Overall,this study resolves the taxonomic assignment of the holotype of O.schmackeri and provides an example for species delimitation using integrative approaches.展开更多
基金supported by Shanghai Science and Technology Commission,China(No.21S11902100)Shanghai Municipal Health Commission Scientific Research Project(No.202140308)+3 种基金Clinical Research Project of Tongji Hospital of Tongji University[No.ITJ(ZD)2209]Shanghai Tongji Hospital National Natural Science Foundation Cultivation Project(No.GJPY2216)Shanghai Medical Innovation Research Special Foundation(No.23Y11908800)CSCO-Haosen Oncology Research Fund(No.Y-HS202301-0096).
文摘Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa(CRPC).Methods:We performed single-cell RNA sequencing(scRNA-seq)on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues,two untreated primary PCa tissues,and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa.We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.Results:scRNA-seq profiles revealed substantial inter-and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors.In the malignant epithelial reservoir,cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors,and distinct transcriptional reprogramming processes were activated,highlighting anti-androgen therapy-induced lineage plasticity.Based on the specifically expressed markers of the epithelial subpopulations,we conducted unsupervised clustering analysis in The Cancer Genome Atlas prostate adenocarcinoma(TCGA-PRAD)cohort and identified three molecularly and clinically distinct subtypes.The C1 subtype,characterized by high enrichment of CRPC-enriched epithelial cells,had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments,such as integrin A3(ITGA3)+integrin B1(ITGB1)inhibition.The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy.The C3 subtype had a favorable prognosis.Conclusions:Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME,and our trichotomic molecular taxonomy could help facilitate precision oncology.
基金supported by the National Natural Sciences Foundation of China (NSFC-31872220, 31572245, 31372164)。
文摘The Odorrana schmackeri sensu la to is a group of cascade frogs that are widely distributed in southern China.However,their taxonomy has long been unresolved and several cryptic species have been reported in the past decade.Previous analyses revealed the existence of three sympatrie species(i.c,O.schmackeri,O.hejiangensis and O.sp2) at the type locality of O.schmackeri(Gaojiayan Town,Yichang City,Hubei Province,China).However,the lack of an original description for the holotype specimen(SMF6241) of O.schmackeri poses a confusing and controversial problem in species nomination within this group.Here,we reevaluate the taxonomic affinities of SMF6241 and examine the distinctness of O.sp2 based on specimens from the type locality.We use integrative approaches that combine morphology with 10 microsatellite loci and bioacoustics.Canonical discriminant analysis of morphological characteristics revealed three distinct groupings(i.e.,O.schmackeri,O.hejiangensis and O.sp2) and attributed SMF6241 to O.schmackeri.Genetic clustering analysis of nuclear DNA also identified three corresponding clusters.In addition,analysis of interspecific variation in morphometrics and acoustics showed divergence between O.sp2 and its sympatric congeners.All lines of evidence from morphological,molecular and bioacoustic approaches suggest the species status of O.sp2,namely Odorrana ichangensis Chen,sp.nov.Overall,this study resolves the taxonomic assignment of the holotype of O.schmackeri and provides an example for species delimitation using integrative approaches.
