Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recogni...Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.展开更多
SSR marker technique was summarized from the aspects of types and genetic characteristics of SSR loci, principles and characteristics of SSR technique, and development of SSR markers. The literatures about the applica...SSR marker technique was summarized from the aspects of types and genetic characteristics of SSR loci, principles and characteristics of SSR technique, and development of SSR markers. The literatures about the applications of SSR markers on germplasm studies of Chinese bayberry were reviewed to provide a refer- ence for related studies.展开更多
基金supported by the National Natural Science Foundation of China(No.82172408)Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)+1 种基金The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100).
文摘Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.
基金Supported by Dr.Startup Funds of Tongren University(trxy DS1303)
文摘SSR marker technique was summarized from the aspects of types and genetic characteristics of SSR loci, principles and characteristics of SSR technique, and development of SSR markers. The literatures about the applications of SSR markers on germplasm studies of Chinese bayberry were reviewed to provide a refer- ence for related studies.
