Little evidence for developmental plasticity of adult hematopoietic stem cells.
To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all.
Wagers
Amy J
AJ
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. awagers@stanford.edu
Sherwood
Richard I
RI
Christensen
Julie L
JL
Weissman
Irving L
IL
D000818:Animals; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002678:Chimera; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology; D007413:Intestinal Mucosa / Q000166:cytology / Q000528:radiation effects; D007420:Intestine, Large / Q000166:cytology; D007421:Intestine, Small / Q000166:cytology; D007668:Kidney / Q000166:cytology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008164:Luminescent Proteins / Q000032:analysis; D008168:Lung / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology; D009206:Myocardium / Q000166:cytology; D009474:Neurons / Q000166:cytology; D010227:Parabiosis; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens