Rb Regulates Interactions between Hematopoietic Stem Cells and Their Bone Marrow Microenvironment
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Hematopoiesis is maintained by stem cells (HSCs) that undergo fate decisions by integrating intrinsic and extrinsic signals, with the latter derived from the bone marrow (BM) microenvironment. Cell-cycle regulation can modulate stem cell fate, but it is unknown whether this represents an intrinsic or extrinsic effector of fate decisions. We have investigated the role of the retinoblastoma protein (RB), a central regulator of the cell cycle, in hematopoiesis. Widespread inactivation of RB in the murine hematopoietic system resulted in profound myeloproliferation. HSCs were lost from the BM due to mobilization to extramedullary sites and differentiation. This phenotype was not intrinsic to HSCs, but, rather, was the consequence of an RB-dependent interaction between myeloid-derived cells and the microenvironment. These findings demonstrate that myeloproliferation may result from perturbed interactions between hematopoietic cells and the niche. Therefore, RB extrinsically regulates HSCs by maintaining the capacity of the BM to support normal hematopoiesis and 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 [34]
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Adult Hematopoiesis is Regulated by TIF1γ, a Repressor of TAL1 and PU.1 Transcriptional Activity
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Cho, J. S., Kook, S. H., Robinson, A. R., Niedernhofer, L. J., & Lee, B.-C. (2013) · Stem Cells · doi:10.1002/stem.1261 · Cited by 27 · see citing works
- Authors
- Walkley, C. R., Shea, J. M., Sims, N. A., Purton, L. E., & Orkin, S. H.
- Affiliations
- Boston Children's Hospital (US)
- The University of Melbourne (AU)
- Harvard University (US)
- Corresponding author
- Orkin, Stuart H.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 129
- Issue
- 6
- Pages
- 1081-1095
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2768301
- OpenAlex
- W2100063372
- Cited by
- 424
- References
- 81
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 3 · 2023: 11 · 2022: 8 · 2021: 15 · 2020: 18 · 2019: 19 · 2018: 25 · 2017: 32 · 2016: 20 · 2015: 29 · 2014: 26 · 2013: 25 · 2012: 36
- FWCI
- 23.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Dana-Farber Cancer Institute
- National Heart, Lung, and Blood Institute (R01HL032259)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- retinoblastoma protein, hematopoietic stem cells, bone marrow microenvironment, hematopoiesis, myeloproliferation, cell cycle regulation, myeloid-derived cells, stem cell fate, extrinsic regulation, stem cell mobilization
- MeSH terms
- Animals, Bone Marrow, Bone Marrow Cells, Cell Cycle, Cell Differentiation, Gene Expression Regulation, Hematopoietic Stem Cells, Models, Biological, Myeloproliferative Disorders, Phenotype, Stem Cells, Time Factors, Retinoblastoma Protein, Gene Deletion, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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