Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood.
Mouse hematopoiesis is initiated by long-term hematopoietic stem cells (HSC) that differentiate into a series of multipotent progenitors that exhibit progressively diminished self-renewal ability. In human hematopoiesis, populations enriched for HSC activity have been identified, as have downstream lineage-committed progenitors, but multipotent progenitor activity has not been uniquely isolated. Previous reports indicate that human HSC are enriched in Lin-CD34+CD38- cord blood and bone marrow and express CD90. We demonstrate that the Lin-CD34+CD38- fraction of cord blood and bone marrow can be subdivided into three subpopulations: CD90+CD45RA-, CD90-CD45RA-, and CD90-CD45RA+. Utilizing in vivo transplantation studies and complementary in vitro assays, we demonstrate that the Lin-CD34+CD38-CD90+CD45RA- cord blood fraction contains HSC and isolate this activity to as few as 10 purified cells. Furthermore, we report the first prospective isolation of a population of candidate human multipotent progenitors, Lin-CD34+CD38-CD90-CD45RA- cord blood.
Majeti
Ravindra
R
Department of Internal Medicine, Division of Hematology, Stanford University, Palo Alto, CA 94304, USA. rmajeti@stanford.edu
Park
Christopher Y
CY
Weissman
Irving L
IL
D049109:Cell Proliferation; D002469:Cell Separation; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood*; D039902:Multipotent Stem Cells / Q000166:cytology*; D018800:Thy-1 Antigens / Q000097:blood*
D018800:Thy-1 Antigens; D017493:Leukocyte Common Antigens