Mitochondrial dynamics govern whole-body regeneration through stem cell pluripotency and mitonuclear balance

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2024-12-13 DOI:10.1038/s41467-024-54720-1

Xue Pan, Yun Zhao, Yucong Li, Jiajia Chen, Wenya Zhang, Ling Yang, Yuanyi Zhou Xiong, Yuqing Ying, Hao Xu, Yuhong Zhang, Chong Gao, Yuhan Sun, Nan Li, Liangyi Chen, Zhixing Chen, Kai Lei

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Abstract

Tissue regeneration is a complex process involving large changes in cell proliferation, fate determination, and differentiation. Mitochondrial dynamics and metabolism play a crucial role in development and wound repair, but their function in large-scale regeneration remains poorly understood. Planarians offer an excellent model to investigate this process due to their remarkable regenerative abilities. In this study, we examine mitochondrial dynamics during planarian regeneration. We find that knockdown of the mitochondrial fusion gene, opa1, impairs both tissue regeneration and stem cell pluripotency. Interestingly, the regeneration defects caused by opa1 knockdown are rescued by simultaneous knockdown of the mitochondrial fission gene, drp1, which partially restores mitochondrial dynamics. Furthermore, we discover that Mito^low stem cells exhibit an enrichment of pluripotency due to their fate choices at earlier stages. Transcriptomic analysis reveals the delicate mitonuclear balance in metabolism and mitochondrial proteins in regeneration, controlled by mitochondrial dynamics. These findings highlight the importance of maintaining mitochondrial dynamics in large-scale tissue regeneration and suggest the potential for manipulating these dynamics to enhance stem cell functionality and regenerative processes.

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组织再生是一个复杂的过程，涉及细胞增殖、命运决定和分化的巨大变化。线粒体动力学和新陈代谢在发育和伤口修复中起着至关重要的作用，但它们在大规模再生过程中的功能仍鲜为人知。浮游动物具有卓越的再生能力，为研究这一过程提供了极佳的模型。在这项研究中，我们考察了浮游动物再生过程中线粒体的动态变化。我们发现，敲除线粒体融合基因opa1会损害组织再生和干细胞多能性。有趣的是，同时敲除线粒体裂解基因 drp1 可以部分恢复线粒体动态，从而挽救 opa1 敲除导致的再生缺陷。此外，我们还发现，米托罗干细胞在早期阶段的命运选择表现出丰富的多能性。转录组分析揭示了线粒体动力学控制的再生过程中代谢和线粒体蛋白的微妙有丝分裂核平衡。这些发现强调了在大规模组织再生过程中保持线粒体动态的重要性，并提出了操纵这些动态以增强干细胞功能和再生过程的潜力。

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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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.