Human primitive hematopoietic progenitor cells are more enriched in KIT(low) cells than in KIT(high) cells

Y. Gunji, M. Nakamura, H. Osawa, K. Nagayoshi, H. Nakauchi, Y. Miura, M. Yanagisawa, T. Suda

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Abstract

To clarify the phenotypes of various classes of human hematopoietic progenitor cells, we used a multicolor staining protocol in conjunction with CD34 and a newly developed mouse antihuman c-kit proto-oncogene product (KIT) monoclonal antibody (MoAb). We characterized three cell fractions in CD34+ cells that express KIT(low) and KIT(high) cells in addition to KIT- cells. A clonogenic assay showed that most granulocyte-macrophage colony-forming cells (GM-CFC) were present in CD34+ KIT(high) populations, whereas erythroid burst-forming cells (BFU-E) were detected mainly in the CD34+ KIT(low) population. CD34+-KIT- fraction contained a small number of BFU-E. Morphologic analysis showed that blast-like cells were more enriched in the CD34+KIT(low) fraction. KIT(low) cells contained CD34+CD38- cells that were considered to be very primitive progenitor cells, as determined by a replating assay. To clarify the biologic differences between both fractions, we examined the more primitive progenitor cell functions by assessing long- term culture-initiating cells (LTC-IC) on the stromal cells. At week 2, more CFC recovered from the culture in the fraction initiated with a CD34+KIT(high) population. However, more LTC-IC were present during weeks 5 to 9 in the CD34+KIT(low) population. These results indicate that primitive progenitors are more enriched in the KIT(low) population and that the KIT(high) population contains many GM-committed progenitor cells. We also showed that anti-KIT MoAb inhibited the ability of CD34+ cells to generate CFC on the stromal layer in the LTC system. This suppressive effect was more evident in the generation of BFU-E by CD34+KIT(low) cells. Moreover, we confirmed that CD34+KIT(high) cells emerged from CD34+KIT(low) cells during coculture with allogeneic stromal cells or from liquid culture in the presence of stem cell factor (SCF), interleukin-6, and erythropoietin. These results emphasize the pivotal role of the KIT and SCF interaction in hematopoiesis and indicate that KIT(low) cells are more primitive than KIT(high) cells.

Original languageEnglish
Pages (from-to)3283-3289
Number of pages7
JournalBlood
Volume82
Issue number11
Publication statusPublished - 1993 Jan 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Gunji, Y., Nakamura, M., Osawa, H., Nagayoshi, K., Nakauchi, H., Miura, Y., Yanagisawa, M., & Suda, T. (1993). Human primitive hematopoietic progenitor cells are more enriched in KIT(low) cells than in KIT(high) cells. Blood, 82(11), 3283-3289.