Thioredoxin-interacting protein regulates hematopoietic stem cell quiescence and mobilization under stress conditions
Open accessAbstract
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.
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Txnip is a thiol-oxidoreductase that controls cellular redox signaling to protect cells from oxidative stress, and regulates hematopoietic stem cell quiescence under stress conditions by stabilizing p53 protein via direct interaction.
“Txnip is a thiol-oxidoreductase that controls cellular redox signaling to protect cells from oxidative stress, and regulates HSC quiescence under stress conditions (34) by stabilizing p53 protein via direct interaction (38).”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [34]
Txnip has a described role in hematopoietic stem cell function, cell-cycle regulation, and stress response.
“This gene was of interest due to its described role in HSC function (34), cell-cycle regulation (35), and stress response (36).”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [34]
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- Authors
- Jeong, M., Piao, Z.-H., Kim, M. S., Lee, S. H., Yun, S., Sun, H.-N., Yoon, S. R., Chung, J. W., Kim, T.-D., Jeon, J. H., Lee, J., Kim, H.-N., Choi, J.-Y., & Choi, I.
- Affiliations
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Dong-A University (KR)
- Kyungpook National University (KR)
- Corresponding author
- Jeong, Mira
- Yun, Sohyun
- Lee, Jiwon
- Choi, Inpyo
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-08
- Volume
- 183
- Issue
- 4
- Pages
- 2495-2505
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2122533032
- Cited by
- 58
- References
- 44
- Citations by year
- 2024: 4 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 7 · 2012: 7
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- KRIBB Repository (submittedVersion)
- Funders
- Korea Research Institute of Bioscience and Biotechnology
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- TXNIP, hematopoietic stem cells, stem cell quiescence, hematopoietic stem cell mobilization, bone marrow microenvironment, Wnt signaling, p21, CXCL12, osteopontin, HSC homing, HSC exhaustion, stress conditions, osteoblastic niche
- MeSH terms
- Animals, Bone Marrow Cells, Carrier Proteins, Cell Movement, Cells, Cultured, Hematopoietic Stem Cells, Mice, Inbred C57BL, Stress, Physiological, Thioredoxins, Time Factors, Signal Transduction, Resting Phase, Cell Cycle, Mice, Knockout, Wnt1 Protein, Mice
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