Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells

Carl R. Walkley, Stuart H. Orkin

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22 Citations (Scopus)

Abstract

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 p21Cip1, p27Kip1, and p16INK4a/p19ARF, 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 RbΔ/Δ bone marrow but a similar contribution to phenotypic HSC populations compared with non-deleted 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.

Original languageEnglish
Pages (from-to)9057-9062
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number24
DOIs
Publication statusPublished - 13 Jun 2006
Externally publishedYes

Keywords

  • Bone marrow transplantation
  • Conditional mutation
  • Retinoblastoma

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