Thioredoxin-interacting protein regulates hematopoietic stem cell quiescence and mobilization under stress conditions.
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.
Jeong
Mira
M
Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea;
Piao
Zheng-Hao
ZH
Kim
Mi Sun
MS
Lee
Suk Hyung
SH
Yun
Sohyun
S
Sun
Hu-Nan
HN
Yoon
Suk Ran
SR
Chung
Jin Woong
JW
Kim
Tae-Don
TD
Jeon
Jun Ho
JH
Lee
Jiwon
J
Kim
Hyun-Nam
HN
Choi
Je-Yong
JY
Choi
Inpyo
I
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics; D013879:Thioredoxins / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D051155:Wnt1 Protein / Q000037:antagonists & inhibitors / Q000502:physiology
D002352:Carrier Proteins; C445672:Txnip protein, mouse; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D013879:Thioredoxins