title: Thioredoxin-interacting protein regulates hematopoietic stem cell quiescence and mobilization under stress conditions.
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.
authors.affiliation: Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea;
authors.forename: Mira
authors.initials: M
authors.lastname: Jeong
authors.forename: Zheng-Hao
authors.initials: ZH
authors.lastname: Piao
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Suk Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Sohyun
authors.initials: S
authors.lastname: Yun
authors.forename: Hu-Nan
authors.initials: HN
authors.lastname: Sun
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.forename: Jin Woong
authors.initials: JW
authors.lastname: Chung
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jeon
authors.forename: Jiwon
authors.initials: J
authors.lastname: Lee
authors.forename: Hyun-Nam
authors.initials: HN
authors.lastname: Kim
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; C445672:Txnip protein, mouse; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D013879:Thioredoxins