Decoding aging-dependent regenerative decline across tissues at single-cell resolution.

Cell stem cell Pub Date : 2023-12-07 Epub Date: 2023-10-27 DOI:10.1016/j.stem.2023.09.014
Yusheng Cai, Muzhao Xiong, Zijuan Xin, Chengyu Liu, Jie Ren, Xiying Yang, Jinghui Lei, Wei Li, Feifei Liu, Qun Chu, Yiyuan Zhang, Jian Yin, Yanxia Ye, Dingyi Liu, Yanling Fan, Shuhui Sun, Yaobin Jing, Qian Zhao, Liyun Zhao, Shanshan Che, Yandong Zheng, Haoteng Yan, Shuai Ma, Si Wang, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu
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Abstract

Regeneration across tissues and organs exhibits significant variation throughout the body and undergoes a progressive decline with age. To decode the relationships between aging and regenerative capacity, we conducted a comprehensive single-cell transcriptome analysis of regeneration in eight tissues from young and aged mice. We employed diverse analytical models to study tissue regeneration and unveiled the intricate cellular and molecular mechanisms underlying the attenuated regenerative processes observed in aged tissues. Specifically, we identified compromised stem cell mobility and inadequate angiogenesis as prominent contributors to this age-associated decline in regenerative capacity. Moreover, we discovered a unique subset of Arg1+ macrophages that were activated in young tissues but suppressed in aged regenerating tissues, suggesting their important role in age-related immune response disparities during regeneration. This study provides a comprehensive single-cell resource for identifying potential targets for interventions aimed at enhancing regenerative outcomes in the aging population.

以单细胞分辨率解码跨组织的衰老依赖性再生衰退。
跨组织和器官的再生在整个身体中表现出显著的变化,并随着年龄的增长而逐渐下降。为了解开衰老和再生能力之间的关系,我们对年轻和衰老小鼠的八种组织的再生进行了全面的单细胞转录组分析。我们采用了多种分析模型来研究组织再生,并揭示了在衰老组织中观察到的衰减再生过程背后的复杂细胞和分子机制。具体而言,我们发现干细胞活动性受损和血管生成不足是导致这种与年龄相关的再生能力下降的主要原因。此外,我们发现了一种独特的Arg1+巨噬细胞亚群,它们在年轻组织中被激活,但在老年再生组织中被抑制,这表明它们在再生过程中与年龄相关的免疫反应差异中发挥着重要作用。这项研究为确定旨在增强老龄化人群再生结果的干预措施的潜在目标提供了全面的单细胞资源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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