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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Terstappen, L. W. Articles by Loken, M. R. Search for Related Content PubMed PubMed Citation Articles by Terstappen, L. W. Articles by Loken, M. R. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells LW Terstappen, S Huang, M Safford, PM Lansdorp and MR Loken Becton Dickinson Immunocytometry Systems, San Jose, CA 95131. Multiparameter flow cytometry was applied on normal human bone marrow (BM) cells to study the lineage commitment of progenitor cells ie, CD34+ cells. Lineage commitment of the CD34+ cells into the erythroid lineage was assessed by the coexpression of high levels of the CD71 antigen, the myeloid lineage by coexpression of the CD33 antigen and the B-lymphoid lineage by the CD10 antigen. Three color immunofluorescence experiments showed that all CD34+ BM cells that expressed the CD71, CD33, and CD10 antigens, concurrently stained brightly with anti-CD38 monoclonal antibodies (MoAbs). In addition, the CD38 antigen was brightly expressed on early T lymphocytes in human thymus, characterized by CD34, CD5, and CD7 expression. Only 1% of the CD34+ cells, 0.01% of nucleated cells in normal BM, did not express the CD38 antigen. The CD34+, CD38- cell population lacked differentiation markers and were homogeneous primitive blast cells by morphology. In contrast the CD34+, CD38 bright cell populations were heterogeneous in morphology and contained myeloblasts and erythroblasts, as well as lymphoblasts. These features are in agreement with properties expected from putative pluripotent hematopoietic stem cells; indeed, the CD34 antigen density decreased concurrently with increasing CD38 antigen density suggesting an upregulation of the CD38 antigen on differentiation of the CD34+ cells. Further evidence for a strong enrichment of early hematopoietic precursors in the CD34+, CD38- cell fraction was obtained from culture experiments in which CD34+ cell fractions with increasing density of the CD38 antigen were sorted singularly and assayed for blast colony formation. On day 14 of incubation, interleukin-3 (IL-3), IL-6, and GM-CSF, G-CSF, and erythropoietin (Epo) were added in each well. Twenty-five percent of the single sorted cells that expressed CD34 but lacked CD38 antigen gave rise to primitive colonies 28 to 34 days after cell sorting. The ability to form primitive colonies decreased rapidly with increasing density of the CD38 antigen. During 120 days of culture, up to five sequential generations of colonies were obtained after replating of the first-generation primitive colonies. This study provides direct evidence for the existence of a single class of progenitors with extensive proliferative capacity in human BM and provides an experimental approach for their purification, manipulation, and further characterization. Volume 77, Issue 6, pp. 1218-1227, 03/15/1991 Copyright © 1991 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Tabatabai, C. Herrmann, G. von Kurthy, M. Mittelbronn, S. Grau, B. Frank, R. Mohle, M. Weller, and W. 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Lund-Johansen Dendritic cell ontogeny: A human dendritic cell lineage of myeloid origin PNAS, November 11, 1997; 94(23): 12551 - 12556. [Abstract] [Full Text] [PDF] L. Humeau, C. Chabannon, M. T. Firpo, P. Mannoni, C. Bagnis, M.-G. Roncarolo, and R. Namikawa Successful Reconstitution of Human Hematopoiesis in the SCID-hu Mouse by Genetically Modified, Highly Enriched Progenitors Isolated From Fetal Liver Blood, November 1, 1997; 90(9): 3496 - 3506. [Abstract] [Full Text] [PDF] S. Ozaki, M. Kosaka, S. Wakatsuki, M. Abe, Y. Koishihara, and T. Matsumoto Immunotherapy of Multiple Myeloma With a Monoclonal Antibody Directed Against a Plasma Cell-Specific Antigen, HM1.24 Blood, October 15, 1997; 90(8): 3179 - 3186. [Abstract] [Full Text] [PDF] D. N. Haylock, M. J. Horsfall, T. L. Dowse, H. S. Ramshaw, S. Niutta, S. Protopsaltis, L. Peng, C. Burrell, I. Rappold, H.-J. Buhring, et al. 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Srour Orderly Process of Sequential Cytokine Stimulation Is Required for Activation and Maximal Proliferation of Primitive Human Bone Marrow CD34+ Hematopoietic Progenitor Cells Residing in G0 Blood, July 15, 1997; 90(2): 658 - 668. [Abstract] [Full Text] [PDF] A.L. Petzer, C.J. Eaves, M.J. Barnett, and A.C. Eaves Selective Expansion of Primitive Normal Hematopoietic Cells in Cytokine-Supplemented Cultures of Purified Cells From Patients With Chronic Myeloid Leukemia Blood, July 1, 1997; 90(1): 64 - 69. [Abstract] [Full Text] [PDF] B. Gahn, C. Schafer, J. Neef, C. Troff, M. Feuring-Buske, W. Hiddemann, and B. Wormann Detection of Trisomy 12 and Rb-Deletion in CD34+ Cells of Patients With B-Cell Chronic Lymphocytic Leukemia Blood, June 15, 1997; 89(12): 4275 - 4281. [Abstract] [Full Text] [PDF] M. Bhatia, J. C. Y. Wang, U. Kapp, D. Bonnet, and J. E. 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