The Journal of immunology (1950), 2009-08, Vol.183 (4), p.2495-2505
2009
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- Autor(en) / Beteiligte
- Titel
- Thioredoxin-Interacting Protein Regulates Hematopoietic Stem Cell Quiescence and Mobilization under Stress Conditions
- Ist Teil von
- The Journal of immunology (1950), 2009-08, Vol.183 (4), p.2495-2505
- Ort / Verlag
- United States: Am Assoc Immnol
- Erscheinungsjahr
- 2009
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1767eISSN: 1550-6606DOI: 10.4049/jimmunol.0804221Titel-ID: cdi_proquest_miscellaneous_67565839
- Format
- –
- Schlagworte
- Animals, Bone Marrow Cells - cytology, Bone Marrow Cells - metabolism, Bone Marrow Cells - physiology, Carrier Proteins - genetics, Carrier Proteins - physiology, Cell Movement - genetics, Cell Movement - physiology, Cells, Cultured, Hematopoietic Stem Cells - cytology, Hematopoietic Stem Cells - metabolism, Hematopoietic Stem Cells - physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Resting Phase, Cell Cycle - genetics, Resting Phase, Cell Cycle - physiology, Signal Transduction - genetics, Stress, Physiological - genetics, Thioredoxins - genetics, Thioredoxins - physiology, Time Factors, Wnt1 Protein - antagonists & inhibitors, Wnt1 Protein - physiology