title: Proliferation and differentiation of highly enriched mouse hematopoietic stem cells and progenitor cells in response to defined growth factors.
abstract: Three distinct hematopoietic populations derived from normal bone marrow were analyzed for their response to defined growth factors. The Thy-1loT- B- G- M-population, composing 0.2% of bone marrow, is 370-fold enriched for pluripotent hematopoietic stem cells. The two other populations, the Thy-1- T- B- G- M- and the predominantly mature Thy-1+ T+ B+ G+ M+ cells, lack stem cells. Thy-1loT- B- G- M- cells respond with a frequency of one in seven cells to IL-3 in an in vitro CFU-C assay, and give rise to many mixed colonies as expected from an early multipotent or pluripotent progenitor. The Thy-1- T- B- G- M- population also contains progenitor cells which responded to IL-3. However, colonies derived from Thy-1- T- B- G- M- cells are almost exclusively restricted to the macrophage/granulocyte lineages. This indicates that IL-3 can stimulate at least two distinct clonogenic early progenitor cells in normal bone marrow: multipotent Thy-1loT- B- G- M- cells and restricted Thy-1- T- B- G- M- cells. Thy-1loT- B- G- M-cells could not be stimulated by macrophage colony-stimulating factor (M-CSF), granulocyte CSF (G-CSF) or IL-5 (Eosinophil-CSF). The hematopoietic precursors that react to these factors are enriched in the Thy-1- T- G- B- M- population. Thus, multipotent and restricted progenitors can be separated on the basis of the expression of the cell surface antigen Thy-1.
authors.affiliation: Lilly Research Laboratories, La Jolla, California 92037.
authors.forename: C E
authors.initials: CE
authors.lastname: Müller-Sieburg
authors.forename: K
authors.initials: K
authors.lastname: Townsend
authors.forename: I L
authors.initials: IL
authors.lastname: Weissman
authors.forename: D
authors.initials: D
authors.lastname: Rennick
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D002469:Cell Separation; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004357:Drug Synergism; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D015848:Interleukin-5; D007378:Interleukins / Q000494:pharmacology; D051379:Mice
chemical_list: D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D015848:Interleukin-5; D007378:Interleukins; D005472:Fluorouracil