Clonal and systemic analysis of long-term hematopoiesis in the mouse.
We have analyzed the temporal in vivo fate of 142 individual stem cell clones in 63 reconstituted mice. Long-term sequential analyses of the four major peripheral blood lineages, obtained from animals engrafted with genetically marked stem cells, indicate that developmental behavior is primarily a function of time. As such, the first 4-6 months post-engraftment is characterized by frequent fluctuations in stem cell proliferation and differentiation behavior. Gradually, a stable hematopoietic system emerges, dominated by a small number of totipotent clones. We demonstrate that single stem cell clones are sufficient to maintain hematopoiesis over the lifetime of an animal and suggest that mono- or oligoclonality may be a hallmark of long-term reconstituted systems. A model is proposed, wherein lineage-restricted differentiation and dramatic clonal flux are consequences of mechanisms acting on an expanding pool of totipotent cells and are not indicative of intrinsically distinct stem cell classes.
Jordan
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CT
Department of Biology, Princeton University, New Jersey 08544.
Lemischka
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D000818:Animals; D002999:Clone Cells / Q000166:cytology; D005260:Female; D005819:Genetic Markers; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D011828:Radiation Chimera; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014185:Transplantation, Isogeneic
D005819:Genetic Markers