Molecular knowledge of human gastric corpus epithelium remains incomplete.Here,by integrated analyses using single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and single-cell assay for transposase accessibl...Molecular knowledge of human gastric corpus epithelium remains incomplete.Here,by integrated analyses using single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and single-cell assay for transposase accessible chromatin sequencing(scATAC-seq)techniques,we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.Specifically,we identified a stem/progenitor cell population in the isthmus of human gastric corpus,where EGF and WNT signaling pathways were activated.Meanwhile,LGR4,but not LGR5,was responsible for the activation of WNT signaling pathway.Importantly,FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells.Finally,we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level,and identified several important cell-type-specific transcription factors.In summary,our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.展开更多
Nanopores are a label-free platform with the ability to detect subtle changes in the activities of individual biomolecules under physiological conditions.Here,we comprehensively review the technological development of...Nanopores are a label-free platform with the ability to detect subtle changes in the activities of individual biomolecules under physiological conditions.Here,we comprehensively review the technological development of nanopores,focusing on their applications in studying the physicochemical properties and dynamic conformations of peptides,individual proteins,protein-protein complexes and protein-DNA complexes.This is followed by a brief discussion of the potential challenges that need to be overcome before the technology can be widely accepted by the scientific community.We believe that with continued refinement of the technology,significant understanding can be gained to help clarify the role of protein activities in the regulation of cellular physiology and pathogenesis.展开更多
基金supported by grants from Beijing Advanced Innovation Center for Genomics(ICG),supported by grants from the National Natural Science Foundation of China(No.81672361)supported by grants from the National Natural Science Foundation of China(No.32100672).
文摘Molecular knowledge of human gastric corpus epithelium remains incomplete.Here,by integrated analyses using single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and single-cell assay for transposase accessible chromatin sequencing(scATAC-seq)techniques,we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.Specifically,we identified a stem/progenitor cell population in the isthmus of human gastric corpus,where EGF and WNT signaling pathways were activated.Meanwhile,LGR4,but not LGR5,was responsible for the activation of WNT signaling pathway.Importantly,FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells.Finally,we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level,and identified several important cell-type-specific transcription factors.In summary,our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
基金supported by the National Key R&D Program of China(2016YFA0501602)a grant from the Beijing Science and Technology Commission(Z151100003915081)
文摘Nanopores are a label-free platform with the ability to detect subtle changes in the activities of individual biomolecules under physiological conditions.Here,we comprehensively review the technological development of nanopores,focusing on their applications in studying the physicochemical properties and dynamic conformations of peptides,individual proteins,protein-protein complexes and protein-DNA complexes.This is followed by a brief discussion of the potential challenges that need to be overcome before the technology can be widely accepted by the scientific community.We believe that with continued refinement of the technology,significant understanding can be gained to help clarify the role of protein activities in the regulation of cellular physiology and pathogenesis.