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线粒体生物能量功能与干细胞分化和细胞重编程中的代谢可塑性

Mitochondrial bioenergetic function and metabolic plasticity in stem cell differentiation and cellular reprogramming.

作者信息

Chen Chien-Tsun, Hsu Shu-Han, Wei Yau-Huei

机构信息

Department of Biochemistry and Molecular Biology, National Yang Ming University, Taipei, Taiwan.

出版信息

Biochim Biophys Acta. 2012 May;1820(5):571-6. doi: 10.1016/j.bbagen.2011.09.013. Epub 2011 Sep 29.

Abstract

BACKGROUND

The self-renewal ability and pluripotent differentiation potential of stem cells hold great promise for regenerative medicine. Many studies focus on the lineage-specific differentiation and expansion of stem cells, but little is known about the regulation of glycolysis and mitochondrial biogenesis and function during these processes. Recent studies have demonstrated a strong correlation between cellular metabolism and the pluripotency and differentiation potential of stem cells, which indicates the importance of bioenergetic function in the regulation of stem cell physiology.

SCOPE OF REVIEW

We summarize recent findings in the control of stem cell competence through the regulation of bioenergetic function in embryonic, hematopoietic, mesenchymal, and induced pluripotent stem cells, and discuss the up-to-date understanding of the molecular mechanisms involved in these biological processes.

MAJOR CONCLUSIONS

It is believed that the metabolic signatures are highly correlated with the stemness status (high glycolytic flux) and differentiation potential (mitochondrial function) of stem cells. Besides, mitochondrial rejuvenation has been observed to participate in the reprogramming process.

GENERAL SIGNIFICANCE

Understanding the metabolic regulation of stem cells will have great value in the characterization and isolation of stem cells with better differentiation potential. It also provides novel strategies of metabolic manipulation to increase the efficiency of cellular reprogramming. This article is part of a Special Issue entitled Biochemistry of Mitochondria, Life and Intervention 2010.

摘要

背景

干细胞的自我更新能力和多能分化潜能为再生医学带来了巨大希望。许多研究聚焦于干细胞的谱系特异性分化和扩增,但对于这些过程中糖酵解以及线粒体生物发生和功能的调控却知之甚少。近期研究表明细胞代谢与干细胞的多能性和分化潜能之间存在紧密关联,这表明生物能量功能在干细胞生理学调控中具有重要意义。

综述范围

我们总结了近期在胚胎干细胞、造血干细胞、间充质干细胞和诱导多能干细胞中通过调控生物能量功能来控制干细胞能力方面的研究发现,并讨论了对这些生物学过程中涉及的分子机制的最新认识。

主要结论

人们认为代谢特征与干细胞的干性状态(高糖酵解通量)和分化潜能(线粒体功能)高度相关。此外,已观察到线粒体年轻化参与重编程过程。

普遍意义

了解干细胞的代谢调控对于鉴定和分离具有更好分化潜能的干细胞具有重要价值。它还为提高细胞重编程效率提供了新的代谢操纵策略。本文是名为《线粒体生物化学、生命与干预2010》特刊的一部分。

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