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

Cited 40 time in scopus
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Title
Thioredoxin-interacting protein regulates hematopoietic stem cell quiescence and mobilization under stress conditions
Author(s)
Mi-Ra Jeong; Z H Piao; Mi-Sun Kim; Suk Hyung Lee; So Hyun Yun; H N Sun; Suk Ran Yoon; J W Chung; Tae-Don Kim; J H Jeon; Ji-Won Lee; H N Kim; J Y Choi; In Pyo Choi
Bibliographic Citation
Journal of Immunology, vol. 183, no. 4, pp. 2495-2505
Publication Year
2009
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
Publisher
Amer Assoc Immunologists
DOI
http://dx.doi.org/10.4049/jimmunol.0804221
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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