Cell Metab：TCA代谢产物能否促进干细胞自我更新也要看“状态”

2016-08-06 佚名生物谷

 近日来自美国加州大学洛杉矶分校的研究人员在国际学术期刊Cell Metabolism上发表了一项最新研究进展，他们发现三羧酸循环中间代谢产物能够影响人类多能干细胞的分化过程，并且这种影响依赖于干细胞的多能性状态。该研究对于如何维持干细胞自我更新抑制分化提供了重要信息。 众所周知多能干细胞能够自我更新或从原始态以及更进一步的分化状态--始发态开始进行分化，目前可以通过特定的培养

近日来自美国加州大学洛杉矶分校的研究人员在国际学术期刊Cell Metabolism上发表了一项最新研究进展，他们发现三羧酸循环中间代谢产物能够影响人类多能干细胞的分化过程，并且这种影响依赖于干细胞的多能性状态。该研究对于如何维持干细胞自我更新抑制分化提供了重要信息。

众所周知多能干细胞能够自我更新或从原始态以及更进一步的分化状态--始发态开始进行分化，目前可以通过特定的培养条件获得始发态多能干细胞。有研究表明增加细胞内α-酮戊二酸（αKG）能够促进原始态小鼠胚胎干细胞的自我更新。但是αKG或αKG /琥珀酸的水平对始发态人类多能干细胞以及小鼠外胚层干细胞分化的影响仍然不清楚。

在这项研究中研究人员对始发态人类多能干细胞以及小鼠外胚层干细胞进行了检测，结果发现αKG增加或αKG /琥珀酸的比例增加都会加速始发态多能干细胞的分化，而琥珀酸水平增加则会导致相反的结果。

有研究证明αKG能够抑制线粒体ATP合酶，还可以调节起表观遗传修饰作用的双加氧酶。研究人员发现线粒体解偶联不会阻碍αKG对始发态人类多能干细胞分化的促进作用，并且αKG能够诱导始发态多能干细胞发生组蛋白和DNA的去甲基化，而琥珀酸则会干扰这一过程。

综上所述这项研究表明αKG对干细胞自我更新和分化过程的影响取决于干细胞的多能性状态。该研究为多能干细胞的实验研究以及临床应用提供了重要信息。

原始出处

Tara TeSlaa1, Andrea C. Chaikovsky2, Inna Lipchina3, Sandra L. Escobar4, Konrad Hochedlinger3, Jing Huang1, 5, 6, Thomas G. Graeber5, 6, 7, 8, Daniel Braas5, 7, Michael A. Teitell.α-Ketoglutarate Accelerates the Initial Differentiation of Primed Human Pluripotent Stem Cells.Cell Metab.2016

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2016-09-27 智智灵药

#MET#

13 0
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2017-05-16 维他命

#CEL#

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2016-09-14 guojianrong

#Meta#

16 0
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2017-01-10 hmwwww

#细胞自我更新#

29 0
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2017-06-23 zhaozhouchifen

#Cell#

20 0
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2016-11-04 xsm926

#自我更新#

23 0
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2017-04-23 paperyu

#TCA#

30 0
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2016-08-08 124987c6m39暂无昵称

#代谢产物#

24 0

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Cell Metab：TCA代谢产物能否促进干细胞自我更新也要看“状态”

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