A high glycolytic flux supports the proliferative potential of murine embryonic stem cells

A high glycolytic flux supports the proliferative potential of murine embryonic stem cells
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DOI:
10.1089/ars.2006.1467
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发表时间:
2007-03-01
影响因子:
6.6
通讯作者:
Beach, David
Beach, David
中科院分区:
生物学2区
文献类型:
--
作者:
Kondoh, Hiroshi;Lleonart, Matilde E.;Beach, David

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胚胎干细胞(ES)是永生的,具有自我更新的能力,同时保持其分化能力。相比之下,大多数原代细胞具有有限的增殖潜力,并且当增殖潜力耗尽时,经历称为衰老的不可逆生长停滞。在原代细胞中,衰老也可以由ES细胞高度不耐受的各种应激触发。在这里,作者报道了小鼠ES细胞的增殖能力与不同糖酵解酶的高活性、糖酵解通量的升高和线粒体耗氧量的降低密切相关。糖酵解通量和ES细胞增殖能力之间的直接关系在糖酵解或ES细胞自我更新被特异性抑制的实验中得到了进一步的说明。先前报道了原代细胞中糖酵解的上调导致寿命延长。作者推测,在小鼠ES细胞中观察到的天然高糖酵解通量可能是其无限增殖潜力的原因。
Embryonic stem (ES) cells are immortal and present the ability to self-renew while retaining their ability to differentiate. In contrast, most primary cells possess a limited proliferative potential, and when this is exhausted, undergo an irreversible growth arrest termed senescence. In primary cells, senescence can be also triggered by a variety of stress to which ES cells are highly refractory. Here the authors report that the proliferative capacity of murine ES cells closely correlates with high activity of different glycolytic enzymes, elevated glycolytic flux, and low mitochondrial oxygen consumption. The direct relation between glycolytic flux and the ability of ES cells to proliferate is further remarked in experiments where glycolysis or ES cell self-renewal was specifically inhibited. It was previously reported that the upregulation of glycolysis in primary cells results in life span extension. The authors hypothesize that the naturally high glycolytic flux observed in murine ES cells can be responsible for their unlimited proliferative potential.