High-level expression of a novel epitope of CD59 identifies a subset of CD34+ bone marrow cells highly enriched for pluripotent stem cells

B. Hill, E. Rozler, M. Travis, S. Chen, A. Zannetino, P. Simmons, A. Galy, B. Chen, R. Hoffman

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20 Citations (Scopus)

Abstract

To further define the hierarchy of human hematopoietic progenitor cells, we have attempted to identify antibodies to cell-surface molecules expressed on CD34+ progenitor cell subsets. Herein we describe the utility of a new monoclonal antibody, HCC-1, which binds to a novel epitope of CD59 differentially expressed among CD34+ progenitor cells. HCC-1 subdivides the adult marrow CD34+ population into HCC-1(high) and HCC-1(low/-) fractions of approximately equal size. Cobblestone area-forming cells (CAFC) in long-term bone marrow culture were enriched 10-30-fold in CD34+HCC-1(high) cells compared with CD34+HCC- 1(low/-) cells and two-fold compared with CD34+ cells. When injected into fetal human bone fragments implanted in SCID mice, the CD34+HCC-1(high) population showed potent engrafting activity leading to the production of myeloid, lymphoid, and erythroid elements, as well as the retention of progenitor cell phenotype. These studies demonstrate that the CD34+HCC-1(high) population contains primitive pluripotent hematopoietic stem cells. No hematopoietic engrafting activity was detected in the CD34+HCC-1(low/-) population. Consistent with this finding, simultaneous five-color now cytometric analysis revealed that HCC-1(high) cells include virtually all CD34+Thy-1+Lin- cells, a cell population previously characterized as highly enriched for primitive pluripotent hematopoietic stem cells. The ability of CD34+ cells divided into subsets by HCC-1 to produce T cells was assessed by transplantation of sorted cells into human fetal thymus implanted into SCID mice. A higher frequency of thymus-engrafting activity was observed in the CD34+HCC-1(high) than in the CD34+HCC-1(low/-) population. Consistent with the limited ability to engraft in the SCID-hu thymus model, the CD34+HCC-1(low/-) population was shown to contain a low frequency of CD34+CD10+ lymphoid progenitor cells. We conclude that the HCC-1 epitope is expressed at high levels on a subset of CD34+ cells that contains virtually all primitive pluripotent hematopoietic stem cells and that the population of CD59 molecules expressed on CD34+ cells is not homogeneous.

Original languageEnglish
Pages (from-to)936-943
Number of pages8
JournalExperimental Hematology
Volume24
Issue number8
Publication statusPublished or Issued - 16 Aug 1996

Keywords

  • Antibody epitope
  • CD59
  • Hematopoietic stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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