Jeong Mira, Piao Zheng-Hao, Kim Mi Sun, Lee Suk Hyung, Yun Sohyun, Sun Hu-Nan, Yoon Suk Ran, Chung Jin Woong, Kim Tae-Don, Jeon Jun Ho, Lee Jiwon, Kim Hyun-Nam, Choi Je-Yong, Choi Inpyo
Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea;
J Immunol. 2009 Aug 15;183(4):2495-505. doi: 10.4049/jimmunol.0804221. Epub 2009 Jul 22.
Hematopoietic stem cells (HSCs) are maintained in a quiescent state in bone marrow (BM) niches by intrinsic and extrinsic signals. The mechanisms regulating the quiescence and mobilization of HSCs, however, remain unclear. In this study, we report that the expression of thioredoxin-interacting protein (TXNIP) is decreased during HSC activation. In Txnip(-/-) mice, the long-term reconstituting HSC population is decreased and exhausted, and its capacity to repopulate is rapidly lost. These effects are associated with hyperactive Wnt signaling, an active cell cycle, and reduced p21 expression under conditions of stress. TXNIP deficiency reduced the CXCL12- and osteopontin-mediated interaction between HSCs and the bone marrow, and impaired homing and retention in the osteoblastic niche, resulting in mobilized HSCs. Therefore, we propose that TXNIP is essential for maintaining HSC quiescence and the interaction between HSCs and the BM niche.
造血干细胞（HSCs）通过内在和外在信号维持在骨髓（BM）微环境中的静止状态。然而，调节HSCs静止和动员的机制仍不清楚。在本研究中，我们报道硫氧还蛋白相互作用蛋白（TXNIP）的表达在HSC激活过程中降低。在Txnip基因敲除小鼠中，长期重建HSC群体减少且耗竭，其重新填充的能力迅速丧失。这些效应与Wnt信号过度活跃、活跃的细胞周期以及应激条件下p21表达降低有关。TXNIP缺乏减少了CXCL12和骨桥蛋白介导的HSCs与骨髓之间的相互作用，并损害了在成骨细胞微环境中的归巢和滞留，导致HSCs动员。因此，我们提出TXNIP对于维持HSC静止以及HSCs与BM微环境之间的相互作用至关重要。
