title: Muscle-derived hematopoietic stem cells are hematopoietic in origin.
abstract: It has recently been shown that mononuclear cells from murine skeletal muscle contain the potential to repopulate all major peripheral blood lineages in lethally irradiated mice, but the origin of this activity is unknown. We have fractionated muscle cells on the basis of hematopoietic markers to show that the active population exclusively expresses the hematopoietic stem cell antigens Sca-1 and CD45. Muscle cells obtained from 6- to 8-week-old C57BL/6-CD45.1 mice and enriched for cells expressing Sca-1 and CD45 were able to generate hematopoietic but not myogenic colonies in vitro and repopulated multiple hematopoietic lineages of lethally irradiated C57BL/6-CD45.2 mice. These data show that muscle-derived hematopoietic stem cells are likely derived from the hematopoietic system and are a result not of transdifferentiation of myogenic stem cells but instead of the presence of substantial numbers of hematopoietic stem cells in the muscle. Although CD45-negative cells were highly myogenic in vitro and in vivo, CD45-positive muscle-derived cells displayed only very limited myogenic activity and only in vivo.
authors.affiliation: Department of Pediatrics, Center for Cell and Gene Therapy, BCM 505, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: McKinney-Freeman
authors.forename: Kathyjo A
authors.initials: KA
authors.lastname: Jackson
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Camargo
authors.forename: Giuliana
authors.initials: G
authors.lastname: Ferrari
authors.forename: Fulvio
authors.initials: F
authors.lastname: Mavilio
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Goodell
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods; D003433:Crosses, Genetic; D017930:Genes, Reporter; D006410:Hematopoiesis / Q000502:physiology* / Q000528:radiation effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D017493:Leukocyte Common Antigens / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology*; D011994:Recombinant Proteins / Q000235:genetics; D014184:Transplantation, Homologous / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D000950:Antigens, Ly; D015415:Biomarkers; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011994:Recombinant Proteins; D017493:Leukocyte Common Antigens; D001616:beta-Galactosidase