Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation.
We found that c-kit-positive, lineage marker-negative, Thy-1lo cells are present in both bone marrow and thymus ("BM c-kit" and "thymus c-kit" cells). Although the two cell types are phenotypically similar, only BM c-kit cells showed the potential to form colonies in vitro as well as in vivo. However, both of them revealed extensive growth and differentiation potential to T cells after direct transfer into an irradiated adult thymus, or a deoxyguanosine-treated fetal thymus. Time course analysis showed that thymus c-kit cells differentiated into CD4CD8 double-positive cells approximately 4 d earlier than BM c-kit cells did. In addition, anti-c-kit antibody blocked T cell generation of BM c-kit cells but not of thymus c-kit cells. Intravenous injection of thymus c-kit resulted in the generation of not only T cells, but B as well as NK1.1+ cells. These data provide evidence that thymus c-kit cells represent common lymphoid progenitors with the differentiation potential to T, B, and possibly NK cells. The c-kit-mediated signaling appears to be essential in the transition from BM c-kit to thymus c-kit cells.
Matsuzaki
Y
Y
Laboratory of Cell Growth and Differentiation, Institute of Physical and Chemical Research (RIKEN), Tsukuba, Japan.
Gyotoku
J
J
Ogawa
M
M
Nishikawa
S
S
Katsura
Y
Y
Gachelin
G
G
Nakauchi
H
H
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001853:Bone Marrow / Q000737:chemistry; D001854:Bone Marrow Cells; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D006410:Hematopoiesis / Q000502:physiology; D006411:Hematopoiesis, Extramedullary / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000737:chemistry / Q000166:cytology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit