Advances in hematopoietic stem cell research through mouse genetics.
OBJECTIVE
Successful bone marrow transplantation involves migration of hematopoietic stem cells through the blood, entering the extravascular hematopoietic cords, lodging in the proper niche, and expanding and differentiating to produce large numbers of mature cells -- all without depletion of the stem cell pool. An additional variable in these processes is the age of both the donor bone marrow and the recipient. Basic stem cell biology and transplant biology aim to uncover the molecular mechanisms controlling these processes.


RESULTS
Mouse genetics is a frequently used tool that allows dissection of individual pathways that influence properties of hematopoietic stem cells. Recently, the conception of a niche has been expanded to include evidence for a vascular and an endosteal niche. Additionally, hematopoietic stem cell interactions within the niche have been further defined, documenting the importance of cell cycle, cell adhesion, response to cytokine stimulation and age-dependent functional changes. A new model for hematopoietic stem cell aging was proposed that supports the hypothesis that stem cell aging is at least partially due to an accumulation of DNA damage leading to exhaustion.


CONCLUSIONS
This review focuses on the last year's progress using mouse genetics as a tool to study intrinsic mechanisms of hematopoietic stem cell biology.
Miller
Alison
A
Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
Van Zant
Gary
G
D000375:Aging / Q000235:genetics*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000639:trends; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D036281:Genetic Research; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D008954:Models, Biological