Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells
Open accessAbstract
Stem cells have been identified as essential for maintaining multiple organ systems, including the hematopoietic system. The distinct cell fates of self-renewal and differentiation of hematopoietic stem cells (HSCs) depend on cell division. Recently, several negative regulators of the cell cycle, such as the cyclin-dependent kinase inhibitors p21 Cip1 , p27 Kip1 , and p16 INK4a /p19 ARF , have been demonstrated to have a role in regulating HSC fate decisions, suggesting that regulation of the G 1 –S phase transition can contribute to HSC self-renewal. Because the retinoblastoma protein, Rb, plays a central role in the regulation of the G 1 –S phase cell cycle, we sought to determine whether it has an intrinsic role in the regulation of HSC fate. Surprisingly, we found that HSC function was essentially normal in the absence of Rb. Rb Δ/Δ HSCs contributed normally to both myeloid and lymphoid lineages in both primary and secondary recipients, and no evidence of transformation was observed. Additionally, we observed a mild myeloid expansion and decrease in mature B cells within the Rb Δ/Δ bone marrow but a similar contribution to phenotypic HSC populations compared with nondeleted bone marrow. The Rb family members p107 and p130 were not deregulated in cells in which Rb had been deleted, as determined by quantitative RT-PCR on the highly enriched stem and primitive progenitor cell lin − c-Kit + Sca-1 + population. These studies demonstrate that Rb is not intrinsically required for self-renewal and multilineage differentiation of adult HSCs.
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Loss of Rb in haematopoietic stem cells does not increase their proliferation in vivo.
“data from several groups indicate that loss of Rb in haematopoietic stem cells (HSCs) does not increase their proliferation”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [33]
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- Authors
- Walkley, C. R., & Orkin, S. H.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Orkin, Stuart H.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-06-13
- Volume
- 103
- Issue
- 24
- Pages
- 9057-9062
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1474009
- OpenAlex
- W1976146328
- Cited by
- 71
- References
- 36
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 6
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- 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
- retinoblastoma protein, hematopoietic stem cells, self-renewal, multilineage differentiation, G1/S transition, p107, p130, p21, p27, myeloid expansion, B-cell depletion, stem cell fate
- MeSH terms
- Animals, Cell Cycle, Cell Differentiation, Female, Hematopoiesis, Hematopoietic Stem Cells, Mice, Inbred C57BL, Mice, Transgenic, Bone Marrow Transplantation, Retinoblastoma Protein, Cell Lineage, Transgenes, Mice
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