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衰老过程中大鼠不同部位脂肪来源间充质干细胞转录组和微小RNA的变化

Alterations in the transcriptome and microRNAs of adipose-derived mesenchymal stem cells from different sites in rats during aging.

作者信息

Su Zhenyang, Xu Tianhua, Sun Jin-Yu, Sun Wei, Kong Xiangqing

机构信息

Department of Cardiology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, People's Republic of China.

出版信息

Am J Physiol Cell Physiol. 2025 Jan 1;328(1):C78-C94. doi: 10.1152/ajpcell.00044.2024. Epub 2024 Nov 4.

Abstract

Aging is an intricate and gradual process characterized by tissue and cellular dysfunction. Adipose-derived mesenchymal stem cells (ADMSCs) experience a functional decline as part of systemic aging. However, the alterations in ADMSCs across various anatomical sites throughout an individual's lifespan remain unclear. To shed light on these changes, we collected white adipose tissue and brown adipose tissue samples from the epididymis, perirenal, inguinal, and scapular regions of young, adult, and aged rats and subsequently isolated ADMSCs for RNA sequencing. As aging progressed, we observed a reduction in the number of ADMSCs at all anatomical sites. Marker genes of ADMSCs from different sites were identified. Aging triggered notable activation of inflammatory and immune responses while diminishing the ADMSC differentiation capacity and ability to maintain a normal tissue morphology. Furthermore, miR-195-5p and miR-497-3p, which promoted cell senescence and apoptosis while inhibiting proliferation and differentiation, were positively correlated with aging. These findings increase our understanding of ADMSC senescence and underscore the unique physiological changes and functions of ADMSCs across different anatomical sites during aging. Dynamic changes in mRNAs and miRNAs of ADMSCs during aging are shown. As aging progressed, we observed a reduction in the number of ADMSCs at all anatomical sites. Aging leads to the activation of inflammatory and cellular dysfunction. miR-195-5p and miR-497-3p are positively correlated with aging, which promoted cell senescence and apoptosis while inhibiting proliferation and differentiation. ADMSCs associated with different anatomical sites have site-specific markers.

摘要

衰老 是一个复杂且渐进的过程,其特征为组织和细胞功能障碍。脂肪来源的间充质干细胞(ADMSC)作为全身衰老的一部分,会经历功能衰退。然而,在个体整个生命周期中,不同解剖部位的ADMSC的变化仍不清楚。为了阐明这些变化,我们从幼年、成年和老年大鼠的附睾、肾周、腹股沟和肩胛区域收集了白色脂肪组织和棕色脂肪组织样本,随后分离出ADMSC进行RNA测序。随着衰老的进展,我们观察到所有解剖部位的ADMSC数量都有所减少。鉴定了来自不同部位的ADMSC的标记基因。衰老引发了炎症和免疫反应的显著激活,同时降低了ADMSC的分化能力和维持正常组织形态的能力。此外,促进细胞衰老和凋亡同时抑制增殖和分化的miR-195-5p和miR-497-3p与衰老呈正相关。这些发现增进了我们对ADMSC衰老的理解,并强调了衰老过程中不同解剖部位ADMSC独特的生理变化和功能。展示了衰老过程中ADMSC的mRNA和miRNA的动态变化。随着衰老的进展,我们观察到所有解剖部位的ADMSC数量都有所减少。衰老导致炎症激活和细胞功能障碍。miR-195-5p和miR-497-3p与衰老呈正相关,它们促进细胞衰老和凋亡,同时抑制增殖和分化。与不同解剖部位相关的ADMSC具有位点特异性标记物。

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