年轻小鼠纤维脂肪祖细胞通过旁分泌作用改善肌肉干细胞的衰老OA
Fibro-adipogenic progenitors from young mice alleviate senescence of muscle stem cells via paracrine regulation
目的 探讨纤维脂肪祖细胞(FAPs)年龄相关变化对肌肉干细胞(MuSCs)衰老的影响.方法 分离年轻和衰老小鼠骨骼肌来源的 MuSCs 和 FAPs,比较年轻与衰老 FAPs 的增殖能力、成纤维分化能力及相关基因表达水平.建立 D-半乳糖(D-gal)诱导的 C2C12 细胞衰老模型和 MuSCs 复制性衰老模型,采用年轻 FAPs 条件培养基进行干预,通过 EdU、SA-β-gal 染色及 qPCR 检测 MuSCs 的增殖及衰老水平.进一步利用不同来源 FAPs 条件培养基处理原代 MuSCs,评价 FAPs 年龄对 MuSCs 功能的影响.结果 与年轻 FAPs 相比,衰老小鼠来源 FAPs 的增殖能力显著降低,成纤维分化能 力 增 强,且 p21 表升高而 IGF1 表达降低.年轻 FAP 条件培养基可显著降低 D-gal 诱导的C2C12 细胞衰老水平,并在复制性衰老 MuSCs 中降低 SA-β-gal 阳性率及 p21 表达,同时恢复细胞增殖能力.此外,年轻 FAP 条件培养基可显著改善衰老小鼠来源 MuSCs 的衰老表型,而衰老 FAP 条件培养基未见明显作用.结论 衰老可显著改变 FAPs 的功能状态,而年轻 FAPs 分泌的因子能够在一定程度上恢复衰老 MuSCs 的增殖能力并降低其衰老水平,提示 FAPs 年龄相关变化是调控肌肉干细胞衰老的重要微环境因素.
Objective To investigate the effects of age-related changes in fibro-adipogenic progenitors(FAPs)on the senescence of muscle stem cells(MuSCs).Methods MuSCs and FAPs were isolated from skeletal muscle of young and aged mice.The proliferative capacity,fibrogenic differentiation potential,and expression of related genes were compared between FAPs from young and aged mice.A D-galactose-induced senescence model in C2C12 cells and a replicative senescence model in MuSCs were established.The conditioned medium of young mice-derived FAPs was used for intervention of the model cells,and the proliferation and senescence of MuSCs were evaluated by EdU incorporation,senescence-associated β-galactosidase(SA-β-gal)staining,and qPCR.In addition,condi-tioned media of FAPs from mice of different ages were used to treat primary MuSCs to evaluate the effect of the age of FAPs on the function of MuSCs.Results Compared with the FAPs from young mice,the FAPs from aged mice exhibited significantly reduced proliferative capacity and enhanced fibrogenic differentiation,accompanied by in-creased expression of p21 and decreased expression of IGF1.The conditioned medium of FAPs from young mice markedly alleviated D-galactose-induced senescence in C2C12 cells.In the MuSC model of replicative senescence,treatment with the conditioned medium of FAPs from young mice decreased the proportion of SA-β-gal-positive cells and reduced p21 expression while restoring proliferative capacity.Furthermore,the conditioned medium of FAPs from young mice significantly ameliorated the senescent phenotype of MuSCs isolated from aged mice,whereas the conditioned medium of FAPs from aged mice showed no obvious effect.Conclusions Aging significantly alters the functional state of FAPs.Factors secreted by FAPs from young mice can partially restore the proliferative capacity of aged MuSCs and reduce their senescence level,which suggests that age-related alterations in FAPs represent a key microenvironmental factor regulating the senescence of muscle stem cells.
朱星雨;肖雨桢;陈运华;孙若曦;孙昭;韩钦;赵春华
中国医学科学院北京协和医学院 基础医学研究所 人工智能细胞医药工程技术交叉创新与临床转化北京市重点实验室,北京 100005中国医学科学院北京协和医学院 基础医学研究所 人工智能细胞医药工程技术交叉创新与临床转化北京市重点实验室,北京 100005中国医学科学院北京协和医学院 基础医学研究所 人工智能细胞医药工程技术交叉创新与临床转化北京市重点实验室,北京 100005中国医学科学院北京协和医学院 基础医学研究所 人工智能细胞医药工程技术交叉创新与临床转化北京市重点实验室,北京 100005中国医学科学院北京协和医学院 北京协和医院 肿瘤内科,北京 100730中国医学科学院北京协和医学院 基础医学研究所 人工智能细胞医药工程技术交叉创新与临床转化北京市重点实验室,北京 100005中国医学科学院北京协和医学院 基础医学研究所 人工智能细胞医药工程技术交叉创新与临床转化北京市重点实验室,北京 100005
生物科学
肌少症肌肉干细胞成纤维/脂肪祖细胞
sarcopeniamuscle stem cellsfibro-adipogenic progenitors
《基础医学与临床》 2026 (6)
747-754,8
国家自然科学基金(82471598)
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