The chiaroscuro stem cell: a unified stem cell theory.
Hematopoiesis has been considered hierarchical in nature, but recent data suggest that the system is not hierarchical and is, in fact, quite functionally plastic. Existing data indicate that engraftment and progenitor phenotypes vary inversely with cell cycle transit and that gene expression also varies widely. These observations suggest that there is no progenitor/stem cell hierarchy, but rather a reversible continuum. This may, in turn, be dependent on shifting chromatin and gene expression with cell cycle transit. If the phenotype of these primitive marrow cells changes from engraftable stem cell to progenitor and back to engraftable stem cell with cycle transit, then this suggests that the identity of the engraftable stem cell may be partially masked in nonsynchronized marrow cell populations. A general model indicates a marrow cell that can continually change its surface receptor expression and thus responds to external stimuli differently at different points in the cell cycle.
Quesenberry
Peter J
PJ
Center for Stem Cell Biology, Roger Williams Medical Center, Providence, RI 02908-4735, USA. pquesenberry@rwmc.org
Colvin
Gerald A
GA
Lambert
Jean-Francois
JF
D000818:Animals; D002415:Cats; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects; D002843:Chromatin / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006085:Graft Survival; D006410:Hematopoiesis / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006413:Hematopoietic System / Q000196:embryology / Q000254:growth & development; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000502:physiology
D002843:Chromatin; D016207:Cytokines; D011956:Receptors, Cell Surface