Hematopoietic Stem Cell Quiescence Is Maintained by Compound Contributions of the Retinoblastoma Gene Family
Open accessAbstract
Individual members of the retinoblastoma (Rb) tumor suppressor gene family serve critical roles in the control of cellular proliferation and differentiation, but the extent of their contributions is masked by redundant and compensatory mechanisms. Here we employed a conditional knockout strategy to simultaneously inactivate all three members, Rb, p107, and p130, in adult hematopoietic stem cells (HSCs). Rb family triple knockout (TKO) mice develop a cell-intrinsic myeloproliferation that originates from hyperproliferative early hematopoietic progenitors and is accompanied by increased apoptosis in lymphoid progenitor populations. Loss of quiescence in the TKO HSC pool is associated with an expansion of these mutant stem cells but also with an enhanced mobilization and an impaired reconstitution potential upon transplantation. The presence of a single p107 allele is sufficient to largely rescue these defects. Thus, Rb family members collectively maintain HSC quiescence and the balance between lymphoid and myeloid cell fates in the hematopoietic system.
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Conditional ablation of all three RB family proteins causes loss of the quiescent HSC pool.
“the quiescent HSC pool is lost when all three RB family proteins are conditionally ablated.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [71]
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- Authors
- Viatour, P., Somervaille, T. C., Venkatasubrahmanyam, S., Kogan, S., McLaughlin, M. E., Weissman, I. L., Butte, A. J., Passegué, E., & Sage, J.
- Affiliations
- University of Liège (BE)
- Stanford Medicine (US)
- University of California, San Francisco (US)
- Massachusetts Eye and Ear Infirmary (US)
- Corresponding author
- Sage, Julien
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 3
- Issue
- 4
- Pages
- 416-428
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2646421
- OpenAlex
- W2062162181
- Cited by
- 178
- References
- 45
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 7 · 2018: 7 · 2017: 12 · 2016: 9 · 2015: 12 · 2014: 18 · 2013: 18 · 2012: 15
- FWCI
- 9.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1750 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- David and Lucile Packard Foundation
- Foundation for the National Institutes of Health
- California Institute for Regenerative Medicine
- Damon Runyon Cancer Research Foundation
- Leukemia and Lymphoma Society
- California Institute of Regenerative Medicine
- National Cancer Institute (T32CA009151, R01CA114102, P01CA049605)
- 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
- hematopoietic stem cells, stem cell quiescence, Rb, p107, p130, conditional knockout mice, myeloproliferation, hematopoietic progenitor cells, apoptosis, lymphoid progenitors, stem cell mobilization, tumor suppressor
- MeSH terms
- Animals, Cell Differentiation, Hematopoietic Stem Cells, Homeostasis, Lymphocytes, Mice, Inbred C57BL, Myeloproliferative Disorders, Retinoblastoma Protein, Apoptosis, Mice, Knockout, Hematopoietic Stem Cell Transplantation, Cell Lineage, Hematopoietic Stem Cell Mobilization, Oligonucleotide Array Sequence Analysis, Myeloid Progenitor Cells, Cell Proliferation, Retinoblastoma-Like Protein p130, Retinoblastoma-Like Protein p107, Mice
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