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Title 

Thioredoxin-interacting protein regulates hematopoietic stem cell quiescence and mobilization under stress conditions

Authors 

Mi-Ra JeongZ H PiaoMi-Sun KimSuk Hyung LeeSo Hyun YunH N SunSuk Ran YoonJ W ChungTae-Don KimJ H JeonJi-Won LeeH N KimJ Y ChoiIn Pyo Choi

Publisher 

American Association of Immunologists

Issue Date 

2009

Citation 

Journal of Immunology, vol. 183, no. 4, pp. 2495-2505

Abstract 

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.

ISSN 

0022-1767

Link 

http://dx.doi.org/10.4049/jimmunol.0804221

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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