Expression of CD33, CD38, and HLA-DR on CD34+ human fetal liver progenitors with a high proliferative potential.
High proliferative-potential colony-forming cells (HPP-CFC) have been identified in the bone marrow of mice and adult humans, and have been characterized as a compartment of primitive progenitors possibly including stem cells. In this report we describe the human fetal liver (FL) as a source of HPP-CFC. These FL HPP-CFC develop in clonal cultures in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) within 3 to 4 weeks. The median frequency of HPP-CFC in FL tissues between 16 and 21 weeks of gestational age was 1 in 3,000 total FL cells. After 4 weeks of growth, FL HPP-CFC grew to a median colony size of 8.3 x 10(4) cells/colony. Using cell-sorting techniques FL HPP-CFC were shown to be predominantly contained in the CD34+ CD33+ CD38- fraction of FL cells. FL HPP-CFC were heterogeneous for HLA-DR expression, and no differences in proliferative capacities were observed between HLA-DR+ and HLA-DR- HPP-CFC. The CD34+ CD33-HLA-DR- CD38- population, previously suggested to contain stem cells, was observed to be very rare in the FL, representing approximately 1 in 1.7 x 10(5) light-density FL cells and containing almost no CFC. Therefore, it is possible that stem cells are contained in the CD33+ fraction of FL cells. Phenotypic characterization of CD34+ CD33+ CD38- lin -LDFL cells showed that these cells are also CD13+, predominantly Thy-1+, CD45RA-, CD45RO-, CD71-, and heterogenoeous for c-kit expression. These data suggest that FL HPP-CFC represent a heterogeneous compartment of primitive myeloid progenitors that may include stem cells.
Muench
M O
MO
Human Immunology Department, DNAX Research Institute, Palo Alto, CA.
Cupp
J
J
Polakoff
J
J
Roncarolo
M G
MG
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002455:Cell Division; D005260:Female; D005333:Fetus / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008099:Liver / Q000166:cytology*; D008562:Membrane Glycoproteins; D011247:Pregnancy; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C571165:Cd33 protein, mouse; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1