Emergence of muscle and neural hematopoiesis in humans.
During human development, hematopoiesis is thought to be compartmentalized to the fetal circulation, liver, and bone marrow. Here, we show that combinations of cytokines together with bone morphogenetic protein-4 and erythropoietin could induce multiple blood lineages from human skeletal muscle or neural tissue. Under defined serum-free conditions, the growth factors requirements, proliferation, and differentiation capacity of muscle and neural hematopoiesis were distinct to that derived from committed hematopoietic sites and were uniquely restricted to CD45(-)CD34(-) cells expressing the prominin AC133. Our study defines epigenetic factors required for the emergence of hematopoiesis from unexpected tissue origins and illustrates that embyronically specified microenvironments do not limit cell fate in humans.
Jay
Karen E
KE
John P. Robarts Research Institute, Developmental Stem Cell Biology, The University of Western Ontario, St. Joseph's Hospital and London Health Sciences, 100 Perth Drive, London, Ontario N6A 5K8, Canada.
Gallacher
Lisa
L
Bhatia
Mickie
M
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D004921:Erythropoietin / Q000494:pharmacology; D006023:Glycoproteins / Q000032:analysis; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D009928:Organ Specificity; D010455:Peptides / Q000032:analysis; D011828:Radiation Chimera; D019089:Stem Cell Factor / Q000494:pharmacology; D014183:Transplantation, Heterologous
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D006023:Glycoproteins; D007377:Interleukin-3; D015850:Interleukin-6; D008565:Membrane Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D017493:Leukocyte Common Antigens