The electron transport chain promotes aspartate synthesis, which is required for cancer cell proliferation. However, it is unclear whether aspartate is limiting in normal stem cells. We found that mouse hematopoietic stem cells (HSCs) depend entirely on cell-autonomous aspartate synthesis, which increases upon HSC activation. Overexpression of the glutamate/aspartate transporter, Glast, or deletion of glutamic-oxaloacetic transaminase 1 (Got1) each increased aspartate levels in HSCs/progenitor cells and increased the function of HSCs but not colony-forming progenitors. Conversely, deletion of Got2 reduced aspartate levels and the function of HSCs but not colony-forming progenitors. Deletion of Got1 and Got2 eliminated HSCs. Isotope tracing showed aspartate was used to synthesize asparagine and purines. Both contributed to increased HSC function as deletion of asparagine synthetase or treatment with 6-mercaptopurine attenuated the increased function of GLAST-overexpressing HSCs. HSC function is thus limited by aspartate, purine, and asparagine availability during hematopoietic regeneration.

电子传递链促进天冬氨酸合成，这是癌细胞增殖所必需的。然而，尚不清楚天冬氨酸是否限制在正常干细胞中。我们发现小鼠造血干细胞 (HSCs) 完全依赖于细胞自主天冬氨酸合成，这会随着 HSC 的激活而增加。谷氨酸/天冬氨酸转运蛋白Glast的过度表达或谷氨酸-草酰乙酸转氨酶 1 ( Got1 ) 的缺失都会增加 HSC/祖细胞中的天冬氨酸水平，并增加 HSC 的功能，但不会增加集落形成祖细胞的功能。相反，Got2的缺失会降低天冬氨酸水平和 HSC 的功能，但不会降低集落形成祖细胞。Got1和Got2的删除消除了 HSC。同位素示踪显示天冬氨酸用于合成天冬酰胺和嘌呤。两者都有助于增加 HSC 功能，因为天冬酰胺合成酶的缺失或用 6-巯基嘌呤处理减弱了 GLAST 过表达 HSC 的功能增加。因此，HSC 功能受到造血再生过程中天冬氨酸、嘌呤和天冬酰胺可用性的限制。