Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information.It is characterized by the ability to visuali...Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information.It is characterized by the ability to visualize changes in molecular information and yields intuitive and vivid visual results.Spatial omics technologies include spatial transcriptomics,spatial proteomics,spatial metabolomics,and other technologies,the most widely used of which are spatial transcriptomics and spatial proteomics.The tumor microenvironment refers to the surrounding microenvironment in which tumor cells exist,including the surrounding blood vessels,immune cells,fibroblasts,bone marrow-derived inflammatory cells,various signaling molecules,and extracellular matrix.A key issue in modern tumor biology is the application of spatial omics to the study of the tumor microenvironment,which can reveal problems that conventional research techniques cannot,potentially leading to the development of novel therapeutic agents for cancer.This paper summarizes the progress of research on spatial transcriptomics and spatial proteomics technologies for characterizing the tumor immune microenvironment.展开更多
Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.H...Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.Here,we focus on two major approaches in spatial transcriptomics(next-generation sequencing-based technologies and image-based technologies),and mass spectrometry imaging technologies used in spatial proteomics and spatial metabolomics.Furthermore,we discuss their applications in neuroscience,including building the brain atlas,uncovering gene expression patterns of neurons for special behaviors,deciphering the molecular basis of neuronal communication,and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders.However,further efforts are still needed toward the integrative application of multi-omics technologies,including the real-time spatial multi-omics analysis in living cells,the detailed gene profile in a whole-brain view,and the combination of functional verification.展开更多
Understanding the specific metabolic changes in multiple regions of the kidney is crucial to revealing the underlying mechanism and developing effective targets for diabetic nephropathy(DN). In this study, integrated ...Understanding the specific metabolic changes in multiple regions of the kidney is crucial to revealing the underlying mechanism and developing effective targets for diabetic nephropathy(DN). In this study, integrated spatially resolved metabolomics and proteomics combined with mass spectrometry imaging(MSI) revealed a multi-scale region profile of the diabetic kidney. Based on anatomic location, spatial metabolomics revealed eight region-specific metabolite biomarkers uniquely localized to kidney segments, which were closely correlated to the clinical parameters of patients with DN. Specifically, treatment with metformin(MET) enriched inosinic acid, adenosine 3′,5′-diphosphate, nicotinamide adenine dinucleotide(NADH), and hydrated NADH(NADHX) levels in the cortex(Cor) and the outer stripe of kidney medulla(OM) anatomical subregions, while in the inner stripe of kidney medulla(IM) segmentation, the p-cresol sulfate level was downregulated. Comparing differently expressed proteins in each region showed that nephrosis 2(Nphs2) was the highest loading feature. A further region-specific analysis of pathway enrichment characteristics indicated that the purine and ether lipid metabolism pathways were enriched in the Cor and OM regions, whereas the pantothenate and coenzyme A(CoA) biosynthesis pathways were mainly enriched in the IM region in response to MET treatment. Taken together, the spatially segregated metabolomics and proteomics studies reveal MET-mediated proteins and function-specific therapeutic pathways related to the anatomical multiregion of diabetic mouse kidneys.展开更多
Recent advances in spatial and single-cell omics have significantly revolutionized biomarker discovery in tumor immunotherapy by addressing critical challenges such as tumor heterogeneity,immune evasion,and variabilit...Recent advances in spatial and single-cell omics have significantly revolutionized biomarker discovery in tumor immunotherapy by addressing critical challenges such as tumor heterogeneity,immune evasion,and variability within the tumor microenvironment(TME).Immunotherapeutic strategies,including immune checkpoint in-hibitors and adoptive T-cell transfer,have demonstrated promising clinical outcomes;however,their efficacy is limited by low response rates and the incidence of immune-related adverse events(irAEs).Therefore,the identification of reliable biomarkers is essential for predicting treatment efficacy,minimizing irAEs,and facili-tating patient stratification.Spatial omics integrates molecular profiling with spatial localization,thereby providing comprehensive insights into the cellular organization and functional states within the TME.By elucidating the spatial patterns of immune cell infiltration and tumor heterogeneity,this approach enhances the prediction of therapeutic responses.Similarly,single-cell omics enables high-resolution analysis of cellular heterogeneity by capturing transcriptomic,epigenomic,and metabolic signatures at the single-cell level.The integrated application of spatial and single-cell omics has enabled the identification of previously undetected biomarkers,including rare immune cell subsets implicated in resistance mechanisms.In addition to spatial transcriptomics(ST),this technological landscape also includes spatial proteomics(SP)and spatial metab-olomics,which further facilitate the study of dynamic tumor-immune interactions.Multi-omics integration provides a comprehensive overview of biomarker landscapes,while the rapid evolution of artificial intelligence(AI)-based approaches enhances the analysis of complex,multidimensional datasets to ultimately enhance pre-dictive potential and clinical utility.Despite substantial progress,several challenges remain in the context of standardization,data integration,and real-time monitoring.Nevertheless,the incorporation of spatial and single-cell omics into biomarker research holds transformative potential for advancing personalized cancer immuno-therapy.These emerging strategies pave the way for the development of innovative diagnostic and therapeutic interventions,thereby enabling precision oncology and improving treatment outcomes across a wide range of tumor profiles.This review aims to provide a comprehensive overview of the integration of spatial omics with single-cell omics in the discovery of biomarkers for tumor immunotherapy.Specifically,it examines the strategies by which these emerging technologies address the challenges related to tumor heterogeneity,immune evasion,and the dynamic nature of the TME.By elaborating on the principles,applications,and clinical potential of these technologies,this review also critically evaluates their limitations,challenges,and the current gaps in clinical translation.展开更多
In a recent study,published in Nature,Nordmann et al.identified Janus kinase inhibitors(JAKi)as a new treatment option for lifethreatening toxic epidermal necrolysis(TEN).They showed this through spatial proteomics on...In a recent study,published in Nature,Nordmann et al.identified Janus kinase inhibitors(JAKi)as a new treatment option for lifethreatening toxic epidermal necrolysis(TEN).They showed this through spatial proteomics on human skin samples combined with in vivo administration of JAKi in individuals with TEN,demonstrating rapid reepithelization and recovery of patients.1 As TEN has a high mortality rate(30-50%),2 this study offers a new avenue for targeted treatment.展开更多
基金supported by Basic and Applied Basic Research Foundation of Guangdong Province(No.2022A1111220217)Medical Scientific Research Foundation of Guangdong Province(Nos.A2023216,A2022124)+3 种基金Science and Technology Program of Guangzhou(Nos.202201010840,202201010810,202102080132,202002030032,202002020023)Health Commission Program of Guangzhou(20212A010021,20201A010081,20211A011116)Science and Technology Project of Panyu,Guangzhou(2022-Z04-009,2022-Z04-090,2022-Z04-072,2021-Z04-013,2020-Z04-026,2019-Z04-02)Scientific Research Project of Guangzhou Panyu Central Hospital(Nos.2022Y002,2021Y004,2021Y002).
文摘Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information.It is characterized by the ability to visualize changes in molecular information and yields intuitive and vivid visual results.Spatial omics technologies include spatial transcriptomics,spatial proteomics,spatial metabolomics,and other technologies,the most widely used of which are spatial transcriptomics and spatial proteomics.The tumor microenvironment refers to the surrounding microenvironment in which tumor cells exist,including the surrounding blood vessels,immune cells,fibroblasts,bone marrow-derived inflammatory cells,various signaling molecules,and extracellular matrix.A key issue in modern tumor biology is the application of spatial omics to the study of the tumor microenvironment,which can reveal problems that conventional research techniques cannot,potentially leading to the development of novel therapeutic agents for cancer.This paper summarizes the progress of research on spatial transcriptomics and spatial proteomics technologies for characterizing the tumor immune microenvironment.
基金supported by the National Natural Science Foundation of China(Grant Nos.:U21A20418,82003727,82273903)l Zhejiang Provincial Natural Science Foundation,China(Grant No.:LQ21H310002).
文摘Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.Here,we focus on two major approaches in spatial transcriptomics(next-generation sequencing-based technologies and image-based technologies),and mass spectrometry imaging technologies used in spatial proteomics and spatial metabolomics.Furthermore,we discuss their applications in neuroscience,including building the brain atlas,uncovering gene expression patterns of neurons for special behaviors,deciphering the molecular basis of neuronal communication,and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders.However,further efforts are still needed toward the integrative application of multi-omics technologies,including the real-time spatial multi-omics analysis in living cells,the detailed gene profile in a whole-brain view,and the combination of functional verification.
基金support from the Program of Natural Science Foundation of State (Grant Nos.81973745 and 82104733)the Hainan Province "Nanhai New Star" Science and Technology Innovation Talent Platform Project by Hainan Provincial Department of Science and Technology (NHXXRCXM202317)the Natural Science Foundation of Heilongjiang Province (YQ2019H030)。
文摘Understanding the specific metabolic changes in multiple regions of the kidney is crucial to revealing the underlying mechanism and developing effective targets for diabetic nephropathy(DN). In this study, integrated spatially resolved metabolomics and proteomics combined with mass spectrometry imaging(MSI) revealed a multi-scale region profile of the diabetic kidney. Based on anatomic location, spatial metabolomics revealed eight region-specific metabolite biomarkers uniquely localized to kidney segments, which were closely correlated to the clinical parameters of patients with DN. Specifically, treatment with metformin(MET) enriched inosinic acid, adenosine 3′,5′-diphosphate, nicotinamide adenine dinucleotide(NADH), and hydrated NADH(NADHX) levels in the cortex(Cor) and the outer stripe of kidney medulla(OM) anatomical subregions, while in the inner stripe of kidney medulla(IM) segmentation, the p-cresol sulfate level was downregulated. Comparing differently expressed proteins in each region showed that nephrosis 2(Nphs2) was the highest loading feature. A further region-specific analysis of pathway enrichment characteristics indicated that the purine and ether lipid metabolism pathways were enriched in the Cor and OM regions, whereas the pantothenate and coenzyme A(CoA) biosynthesis pathways were mainly enriched in the IM region in response to MET treatment. Taken together, the spatially segregated metabolomics and proteomics studies reveal MET-mediated proteins and function-specific therapeutic pathways related to the anatomical multiregion of diabetic mouse kidneys.
基金support from Hangzhou Institute of Medicine,China(No.2024ZZBS11)Chinese Academy of Sciences,China Postdoctoral Science Foundation(No.2024M763331)+1 种基金National Oncology Clinical Key Specialty of China(No.2023-GJZK-001)Zhejiang Provincial Natural Science Foundation of China(No.LQN25H160009).
文摘Recent advances in spatial and single-cell omics have significantly revolutionized biomarker discovery in tumor immunotherapy by addressing critical challenges such as tumor heterogeneity,immune evasion,and variability within the tumor microenvironment(TME).Immunotherapeutic strategies,including immune checkpoint in-hibitors and adoptive T-cell transfer,have demonstrated promising clinical outcomes;however,their efficacy is limited by low response rates and the incidence of immune-related adverse events(irAEs).Therefore,the identification of reliable biomarkers is essential for predicting treatment efficacy,minimizing irAEs,and facili-tating patient stratification.Spatial omics integrates molecular profiling with spatial localization,thereby providing comprehensive insights into the cellular organization and functional states within the TME.By elucidating the spatial patterns of immune cell infiltration and tumor heterogeneity,this approach enhances the prediction of therapeutic responses.Similarly,single-cell omics enables high-resolution analysis of cellular heterogeneity by capturing transcriptomic,epigenomic,and metabolic signatures at the single-cell level.The integrated application of spatial and single-cell omics has enabled the identification of previously undetected biomarkers,including rare immune cell subsets implicated in resistance mechanisms.In addition to spatial transcriptomics(ST),this technological landscape also includes spatial proteomics(SP)and spatial metab-olomics,which further facilitate the study of dynamic tumor-immune interactions.Multi-omics integration provides a comprehensive overview of biomarker landscapes,while the rapid evolution of artificial intelligence(AI)-based approaches enhances the analysis of complex,multidimensional datasets to ultimately enhance pre-dictive potential and clinical utility.Despite substantial progress,several challenges remain in the context of standardization,data integration,and real-time monitoring.Nevertheless,the incorporation of spatial and single-cell omics into biomarker research holds transformative potential for advancing personalized cancer immuno-therapy.These emerging strategies pave the way for the development of innovative diagnostic and therapeutic interventions,thereby enabling precision oncology and improving treatment outcomes across a wide range of tumor profiles.This review aims to provide a comprehensive overview of the integration of spatial omics with single-cell omics in the discovery of biomarkers for tumor immunotherapy.Specifically,it examines the strategies by which these emerging technologies address the challenges related to tumor heterogeneity,immune evasion,and the dynamic nature of the TME.By elaborating on the principles,applications,and clinical potential of these technologies,this review also critically evaluates their limitations,challenges,and the current gaps in clinical translation.
文摘In a recent study,published in Nature,Nordmann et al.identified Janus kinase inhibitors(JAKi)as a new treatment option for lifethreatening toxic epidermal necrolysis(TEN).They showed this through spatial proteomics on human skin samples combined with in vivo administration of JAKi in individuals with TEN,demonstrating rapid reepithelization and recovery of patients.1 As TEN has a high mortality rate(30-50%),2 this study offers a new avenue for targeted treatment.
