Genetic manipulation of human pluripotent stem cells(hPSCs)provides a powerful tool for modeling diseases and developing future medicine.Recently a number of independent genome-editing techniques were developed,includ...Genetic manipulation of human pluripotent stem cells(hPSCs)provides a powerful tool for modeling diseases and developing future medicine.Recently a number of independent genome-editing techniques were developed,including plasmid,bacterial artificial chromosome,adeno-associated virus vector,zinc finger nuclease,transcription activator-like effecter nuclease,and helper-dependent adenoviral vector.Gene editing has been successfully employed in different aspects of stem cell research such as gene correction,mutation knock-in,and establishment of reporter cell lines(Raya et al.,2009;Howden et al.,2011;Li et al.,2011;Liu et al.,2011b;Papapetrou et al.,2011;Sebastiano et al.,2011;Soldner et al.,2011;Zou et al.,2011a).These techniques combined with the utility of hPSCs will significantly influence the area of regenerative medicine.展开更多
Dear Editor Human pluripotent stem cells including human embryonic stem cells （ESCs） and induced pluripotent stem cells （iPSCs） are cells displaying abilities of unlimited self-renewal and differentiation into any...Dear Editor Human pluripotent stem cells including human embryonic stem cells （ESCs） and induced pluripotent stem cells （iPSCs） are cells displaying abilities of unlimited self-renewal and differentiation into any somatic cell type. These unique properties make them increasingly attractive for novel applications in disease modeling, drug discovery, and cell therapy （Buganim et al., 2014; Liu et al., 2011; Liu et al., 2012; Sanchez Alvarado and Yamanaka, 2014）. Moreover, iPSCs hold great potential for personalized cell therapy as they avoid some of the ethical concerns as well as the immunological rejection issues ascribed to ESCs.展开更多
The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underly...The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underlying human synovial aging remains poorly characterized.Here,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged individuals.By delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged MSCs.Moreover,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue fibrosis.In particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged synovium.In human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged donors.These data indicate an important role of FOXO1 in the regulation of human synovial aging.Overall,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.展开更多
文摘Genetic manipulation of human pluripotent stem cells(hPSCs)provides a powerful tool for modeling diseases and developing future medicine.Recently a number of independent genome-editing techniques were developed,including plasmid,bacterial artificial chromosome,adeno-associated virus vector,zinc finger nuclease,transcription activator-like effecter nuclease,and helper-dependent adenoviral vector.Gene editing has been successfully employed in different aspects of stem cell research such as gene correction,mutation knock-in,and establishment of reporter cell lines(Raya et al.,2009;Howden et al.,2011;Li et al.,2011;Liu et al.,2011b;Papapetrou et al.,2011;Sebastiano et al.,2011;Soldner et al.,2011;Zou et al.,2011a).These techniques combined with the utility of hPSCs will significantly influence the area of regenerative medicine.
文摘Dear Editor Human pluripotent stem cells including human embryonic stem cells （ESCs） and induced pluripotent stem cells （iPSCs） are cells displaying abilities of unlimited self-renewal and differentiation into any somatic cell type. These unique properties make them increasingly attractive for novel applications in disease modeling, drug discovery, and cell therapy （Buganim et al., 2014; Liu et al., 2011; Liu et al., 2012; Sanchez Alvarado and Yamanaka, 2014）. Moreover, iPSCs hold great potential for personalized cell therapy as they avoid some of the ethical concerns as well as the immunological rejection issues ascribed to ESCs.
基金supported by the National Natural Science Foundation of China(92149301,81921006,82125011)the National Key Research and Development Program of China(2022YFA1103700,2022YFA1103800,2020YFA0804000,2020YFA0112200,2021YFF1201000,the STI2030-Major Projects-2021ZD0202400)+8 种基金the National Natural Science Foundation of China(92168201,91949209,92049304,92049116,32121001,82192863,82122024,82071588,32000500,82271600)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Project for Technology Development of Beijing-affiliated Medical Research Institutes(11000023T000002036310)Youth Innovation Promotion Association of CAS(E1CAZW0401,2023092,2022083)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101)New Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045)Excellent Young Talents Program of Capital Medical University(12300927)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001).
文摘The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underlying human synovial aging remains poorly characterized.Here,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged individuals.By delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged MSCs.Moreover,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue fibrosis.In particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged synovium.In human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged donors.These data indicate an important role of FOXO1 in the regulation of human synovial aging.Overall,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.
