Identification of Hematopoietic Stem Cells in Human and Mouse
The first isolation of hematopoietic stem cells (HSC) required quantitative clonal assays for every blood cell progenitor type (T, B, myeloerythroid) and methods to sort cells based on their unique expression profiles, as determined by cell surface markers. Using this approach, both mouse and human hematopoietic stem cells were prospectively isolated. All HSC activity in adult mouse bone marrow (BM) was shown to be contained in a population marked by the composite phenotype of c-Kit+, Thy-1.1lo, lineage marker-, and Sca-1+ (designated KTLS). These KTLS hematopoietic stem cells in mice transplanted at the single-cell level gave rise to lifelong hematopoiesis, including a steady state of 20 to 100,000 HSC and over 109 blood cells produced daily.
Mouse Hematopoietic Stem Cell Identification
Human Hematopoietic Stem Cell Identification
In humans, the isolation of a lin- CD34+CD90+ progenitor cell resulted in the purification of a homogeneous HSC population. The critical test for HSCs is in their ability to clinically rescue myelo-ablated hosts from hematopoietic failure, and establish long-term multi-hematopoietic lineage reconstitution. Clinical implantation of HSCs into cancer patients has led to stable grafts depleted of contaminating hematopoietic cells and resident or metastasized malignant cells. The continued identification of novel hematopoietic stem cell markers will enable improved efficiency in the purification of HSCs for the treatment of disease.
Phenotypes of Hematopoietic Stem Cells
The tables below outline the accepted phenotypes for the isolation of human and mouse hematopoietic stem cells and developmental intermediates of the lymphoid and myeloid lineages.
|Multipotent, CD34/Flk2 Series|
|Multipotent, SLAM Series|
|Hematopoietic Stem Cell||Lin-CD34+CD38-CD90+CD45RA-|
|Common Myeloid Progenitor||Lin-CD34+CD38+IL-3RαloCD45RA-|
|Common Lymphoid Progenitor||Lin-CD34+CD38+CD10+|
The promise of human induced pluripotent stem cells for research and therapy. Nishikawa S, Goldstein RA, Nierras CR. Nat Rev Mol Cell Biol. 2008 Sep;9(9):725-9. Review.