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Functional characterization of a novel hematopoietic stem cell and its place in the c-kit maturation pathway in bone marrow cell development

  1. Author:
    Ortiz, M.
    Wine, J. W.
    Lohrey, N.
    Ruscetti, F. W.
    Spence, S. E.
    Keller, J. R.

  2. Author Address

    Keller JR SAIC Frederick, Intramural Res Support Program Frederick, MD 21702 USA SAIC Frederick, Intramural Res Support Program Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol Frederick, MD 21702 USA
    1. Year: 1999
  2. Journal: Immunity
    1. 10
    2. 2
    3. Pages: 173-182
  4. Type of Article: Article
  1. Abstract:

    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. [References: 33]

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