Lymphocyte development from stem cells.
Highly enriched pluripotent and multipotent hematopoietic stem cells (HSCs) are isolated from bone marrow and fetal liver as Thy-1loLin-Sca-1+ cells. Pluripotent HSCs express c-kit receptor on their surface, but the generation and proliferation of early fetal HSCs take place in the absence of steel factor. T precursor cells migrate into the fetal thymus by chemotactic mechanism. CD4lo precursors represent a newly defined phase of T-cell development in the thymus between the bone marrow-derived stem cells and the CD4-8- intrathymic precursors. Only fetal, but not adult, HSCs have the capacity to differentiate into V gamma 3+ and V gamma 4+ T cells under the fetal thymic microenvironment, and HSC themselves may lose some of their developmental potential during ontogeny. It is postulated that HSCs are the locus of a complicated but precise developmental clock that may determine both the time-dependent closure of some gene loci (e.g. V gamma 3 and V gamma 4 T cell receptor, and embryonic and fetal globin) and the activation of others (e.g. the N nucleotide insertion machinery).
Ikuta
K
K
Howard Hughes Medical Institute, Standord University School of Medicine, California 94305.
Uchida
N
N
Friedman
J
J
Weissman
I L
IL
D000818:Animals; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D016298:Hematopoietic Cell Growth Factors / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit