Genetic models to study quiescent stem cells and their niches

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5 Scopus citations


Hematopoietic stem cells (HSC) have been defined by their ability to establish long-term hematopoiesis in myelo-ablated hosts. Prospective isolation using combinations of cell-surface markers andor dye exclusion can yield highly purified and nearly homogeneous phenotypically defined cells that repopulate irradiated hosts. Although highly informative, these types of analyses may not necessarily reflect ongoing homeostatic hematopoiesis. HSCs are also described as being quiescent. This has been demonstrated by cell cycle analysis of phenotypically defined HSCs. Some studies have challenged the existence of truly quiescent HSCs, suggesting that they continuously cycle, albeit with very slow kinetics. Here we present a pulse-chase system based on the controllable incorporation of H2B-GFP into nucleosomes, which allows the identification, purification, and functional analysis of viable label-retaining cells. Our data complement and extend recent studies using similar strategies. These, together with our present studies, find a rare, quiescent or dormant subset within the population of stringently defined HSC phenotypes. To date, three types of niches, endosteal, vascular, and reticular, have been described; herein we review the cellular and spatial nature of these microenvironments. We propose that HSC label-retention combined with genetically manipulated stem cell niches will allow us to determine their anatomical architecture, to address HSC cell fate proliferation kinetics, and to begin to dissect the molecular cross talk among stem cells and niche cells in vivo during both normal and perturbed homeostasis.

Original languageEnglish
Title of host publicationHematopoietic Stem Cells VII
PublisherBlackwell Publishing Inc.
Number of pages10
ISBN (Print)9781573317610
StatePublished - 2009

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Bone marrow
  • Endosteum
  • Endothelial
  • Hematopoietic stem cell
  • Label-retaining cell
  • Niche
  • Osteoblast
  • Pulse-chase
  • Quiescence
  • Reticular cell
  • Self-renewal
  • Tet-OnOff system
  • Vascular


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