Abstract:
Lysosomes play crucial roles in regulating cell metabolism, and K+ channels are critical for controlling various aspects of lysosomal function. Additionally, lysosomal activity is essential for maintaining the quiescence of hematopoietic stem cells (HSCs) under both steady-state and stress conditions. Tmem175 is a lysosomal potassium channel protein. To further investigate the role of K+ channels in HSCs, our study employed knockout mice to examine the function of Tmem175. Our research findings demonstrate that the deletion of Tmem175 does not disrupt the functionality of HSCs in both stable and stressed conditions, including irradiation and intraperitoneal 5-FU injections. However, we did observe that the absence of Tmem175 impairs the long-term differentiation capacity of HSCs into myeloid differentiated subpopulation cells(In this paper, it is referred to simply as M cells)in HSC transplantation test, while promoting their differentiation into T cells. This suggests that Tmem175 plays a role in the lineage differentiation of HSCs without being essential for their self-renewal or long-term regenerative capabilities.
摘要:
溶酶体在调节细胞代谢中起着至关重要的作用,和K+通道对于控制溶酶体功能的各个方面至关重要。此外,溶酶体活性对于在稳态和应激条件下维持造血干细胞(HSC)的静止至关重要。Tmem175是溶酶体钾离子通道蛋白。为了进一步研究K+通道在HSCs中的作用,我们的研究使用基因敲除小鼠来检查Tmem175的功能.我们的研究结果表明,Tmem175的缺失不会破坏HSC在稳定和应激条件下的功能。包括照射和腹膜内注射5-FU。然而,我们确实观察到Tmem175的缺失会损害HSCs向髓样分化亚群细胞的长期分化能力(本文,在HSC移植试验中简称为M细胞),同时促进它们分化为T细胞。这表明Tmem175在HSC的谱系分化中起作用,而不是它们的自我更新或长期再生能力所必需的。