造血干细胞对高能和氧化压力非常敏感，对它们的静止与增殖之间的平衡进行调控是响应代谢压力、同时保持其长期再生能力所需要的。三项新的研究表明，肿瘤抑制因子和代谢传感器Lkb1在维持造血细胞的能量平衡中起关键作用。Lkb1被发现是细胞周期调控及能量平衡所必需的，造血干细胞对Lkb1的依赖性要强于对任何其他造血细胞的依赖性。
推荐原文出处：
Nature doi:10.1038/nature09571
Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells
Daisuke Nakada1,2, Thomas L. Saunders2,3 " Sean J. Morrison1,2
1.Howard Hughes Medical Institute, Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA
2.Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-2216, USA
3.Transgenic Animal Model Core, University of Michigan, Ann Arbor, Michigan 48109-2216, USA
Top of pageAbstractLittle is known about metabolic regulation in stem cells and how this modulates tissue regeneration or tumour suppression. We studied the Lkb1 tumour suppressor and its substrate AMP-activated protein kinase (AMPK), kinases that coordinate metabolism with cell growth. Deletion of the Lkb1 (also called Stk11) gene in mice caused increased haematopoietic stem cell (HSC) division, rapid HSC depletion and pancytopenia. HSCs depended more acutely on Lkb1 for cell-cycle regulation and survival than many other haematopoietic cells. HSC depletion did not depend on mTOR activation or oxidative stress. Lkb1-deficient HSCs, but not myeloid progenitors, had reduced mitochondrial membrane potential and ATP levels. HSCs deficient for two catalytic α-subunits of AMPK (AMPK-deficient HSCs) showed similar changes in mitochondrial function but remained able to reconstitute irradiated mice. Lkb1-deficient HSCs, but not AMPK-deficient HSCs, exhibited defects in centrosomes and mitotic spindles in culture, and became aneuploid. Lkb1 is therefore required for HSC maintenance through AMPK-dependent and AMPK-independent mechanisms, revealing differences in metabolic and cell-cycle regulation between HSCs and some other haematopoietic progenitors.
