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Noncanonical NF-κB Signaling Regulates Hematopoietic Stem Cell Self-Renewal and Microenvironment Interactions

Zhao, Chen, Xiu, Yan, Ashton, John, Xing, Lianping, Morita, Yoshikazu, Jordan, Craig T., Boyce, Brendan F.·2012·Stem Cells
DOI 10.1002/stem.1050PMC PMC3602314
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Abstract

RelB and nuclear factor κB (NF-κB2) are the main effectors of NF-κB noncanonical signaling and play critical roles in many physiological processes. However, their role in hematopoietic stem/progenitor cell (HSPC) maintenance has not been characterized. To investigate this, we generated RelB/NF-κB2 double-knockout (dKO) mice and found that dKO HSPCs have profoundly impaired engraftment and self-renewal activity after transplantation into wild-type recipients. Transplantation of wild-type bone marrow cells into dKO mice to assess the role of the dKO microenvironment showed that wild-type HSPCs cycled more rapidly, were more abundant, and had developmental aberrancies: increased myeloid and decreased lymphoid lineages, similar to dKO HSPCs. Notably, when these wild-type cells were returned to normal hosts, these phenotypic changes were reversed, indicating a potent but transient phenotype conferred by the dKO microenvironment. However, dKO bone marrow stromal cell numbers were reduced, and bone-lining niche cells supported less HSPC expansion than controls. Furthermore, increased dKO HSPC proliferation was associated with impaired expression of niche adhesion molecules by bone-lining cells and increased inflammatory cytokine expression by bone marrow cells. Thus, RelB/NF-κB2 signaling positively and intrinsically regulates HSPC self-renewal and maintains stromal/osteoblastic niches and negatively and extrinsically regulates HSPC expansion and lineage commitment through the marrow microenvironment. Disclosure of potential conflicts of interest is found at the end of this article.

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Metadata

Authors
Zhao, C., Xiu, Y., Ashton, J., Xing, L., Morita, Y., Jordan, C. T., & Boyce, B. F.
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2012-03-22
Volume
30
Issue
4
Pages
709-718
ISSN
  • 1066-5099
  • 1549-4918
DOI
10.1002/stem.1050
PMC
PMC3602314
Cited by
65
References
5
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Funders
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR043510)
  • National Institutes of Health

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CoChat. (2026). Citation check: Noncanonical NF-κB Signaling Regulates Hematopoietic Stem Cell Self-Renewal and Microenvironment Interactions. https://app.cochat.ai/papers/10.1002/stem.1050
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Zhao, C., Xiu, Y., Ashton, J., Xing, L., Morita, Y., Jordan, C. T., & Boyce, B. F. (2012). Noncanonical NF-κB Signaling Regulates Hematopoietic Stem Cell Self-Renewal and Microenvironment Interactions. Stem Cells. https://doi.org/10.1002/stem.1050