Functional Characterization of a Novel Hematopoietic Stem Cell and Its Place in the c-Kit Maturation Pathway in Bone Marrow Cell Development

• Published in: Immunity (Cambridge, Mass.) Mass.), 1999-02, Vol.10 (2), p.173-182
• Main Authors: Ortiz, Mariaestela, Wine, John W, Lohrey, Nancy, Ruscetti, Francis W, Spence, Sally E, Keller, Jonathan R
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - physiology; Cell Line; Cell Separation; Colony-Forming Units Assay; Flow Cytometry; Hematopoietic Stem Cells - physiology; Mice; Mice, Inbred C57BL; Polymerase Chain Reaction; Proto-Oncogene Proteins c-kit - physiology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80018-7

While the majority of purified pluripotential hematopoietic stem cells (PHSC) express c-Kit, the receptor for steel factor, we have phenotypically and functionally separated a distinct class of PHSC that does not express c-Kit. In contrast to c-Kit-postive (c-Kit pos) PHSC, the c-Kit-negative (c-Kit neg) PHSC do not proliferate in response to multiple hematopoietic growth factors in vitro and do not radioprotect or form macroscopic spleen colonies (CFU-s) when transplanted into lethally irradiated recipients. However, the c-Kit neg PHSC show delayed or slow reconstitution kinetics when cotransplanted with radioprotective bone marrow cells. c-Kit neg PHSCs cells can give rise to c-Kit pos cells with CFU-s activity, radioprotective activity, and PHSC activity. Thus, constituitive hematopoiesis is maintained by c-Kit pos PHSCS cells that are recruited from a more primitive quiescent c-Kit neg PHSC population, which represents a critical developmental stage in definitive hematopoiesis.