Extracellular arginine is required but the arginine transporter CAT3 (Slc7a3) is dispensable for mouse normal and malignant hematopoiesis.

Amino acid-mediated metabolism is one of the key catabolic and anabolic processes involved in diverse cellular functions. However, the role of the semi-essential amino acid arginine in normal and malignant hematopoietic cell development is poorly understood. Here we report that a continuous supply of exogenous arginine is required for the maintenance/function of normal hematopoietic stem cells (HSCs). Surprisingly, knockout of Slc7a3 (CAT3), a major L-arginine transporter, does not affect HSCs in steady-state or under stress. Although Slc7a3 is highly expressed in naïve and activated CD8 T cells, neither T cell development nor activation/proliferation is impacted by Slc7a3 depletion. Furthermore, the Slc7a3 deletion does not attenuate leukemia development driven by Pten loss or the oncogenic Ptpn11E76K mutation. Arginine uptake assays reveal that L-arginine uptake is not disrupted in Slc7a3 knockout cells. These data suggest that extracellular arginine is critically important for HSCs, but CAT3 is dispensable for normal hematopoiesis and leukemogenesis.

氨基酸介导的代谢是参与多种细胞功能的关键分解代谢和合成代谢过程之一。然而，半必需氨基酸精氨酸在正常和恶性造血细胞发育中的作用知之甚少。在此我们报道，正常造血干细胞（HSCs）的维持/功能需要外源性精氨酸的持续供应。令人惊讶的是，主要的L -精氨酸转运体Slc7a3（CAT3）的敲除在稳态或应激条件下并不影响HSCs。尽管Slc7a3在初始和活化的CD8 T细胞中高表达，但Slc7a3的缺失既不影响T细胞发育，也不影响其活化/增殖。此外，Slc7a3的缺失不会减弱由Pten缺失或致癌的Ptpn11E76K突变驱动的白血病发展。精氨酸摄取实验表明，在Slc7a3敲除细胞中L -精氨酸摄取未受干扰。这些数据表明，细胞外精氨酸对HSCs至关重要，但CAT3对正常造血和白血病发生是可有可无的。