Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 2014 May 1;509(7498):49-54. doi: 10.1038/nature13035. Epub 2014 Mar 9.
Many aspects of cellular physiology remain unstudied in somatic stem cells, for example, there are almost no data on protein synthesis in any somatic stem cell. Here we set out to compare protein synthesis in haematopoietic stem cells (HSCs) and restricted haematopoietic progenitors. We found that the amount of protein synthesized per hour in HSCs in vivo was lower than in most other haematopoietic cells, even if we controlled for differences in cell cycle status or forced HSCs to undergo self-renewing divisions. Reduced ribosome function in Rpl24(Bst/+) mice further reduced protein synthesis in HSCs and impaired HSC function. Pten deletion increased protein synthesis in HSCs but also reduced HSC function. Rpl24(Bst/+) cell-autonomously rescued the effects of Pten deletion in HSCs; blocking the increase in protein synthesis, restoring HSC function, and delaying leukaemogenesis. Pten deficiency thus depletes HSCs and promotes leukaemia partly by increasing protein synthesis. Either increased or decreased protein synthesis impairs HSC function.
许多细胞生理学方面的内容在体干细胞中仍未得到研究，例如，几乎没有任何关于任何体干细胞中蛋白质合成的数据。在这里，我们着手比较造血干细胞（HSCs）和受限造血祖细胞中的蛋白质合成。我们发现，体内 HSCs 每小时合成的蛋白质数量低于大多数其他造血细胞，即使我们控制了细胞周期状态的差异或强制 HSCs 进行自我更新分裂。Rpl24（Bst/+）小鼠中核糖体功能的降低进一步降低了 HSCs 中的蛋白质合成并损害了 HSC 功能。Pten 缺失增加了 HSCs 中的蛋白质合成，但也降低了 HSC 功能。Rpl24（Bst/ +）细胞自主地挽救了 Pten 缺失对 HSCs 的影响；阻断蛋白质合成的增加，恢复 HSC 功能，并延迟白血病的发生。因此，Pten 缺失通过增加蛋白质合成来耗尽 HSCs 并促进白血病的发生。无论是增加还是减少蛋白质合成都会损害 HSC 功能。
