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  • 1
    Online Resource
    Online Resource
    Asymmetric Cell Divisions in Hematopoietic Stem Cells
    Wiley ; 1999
    In:  Annals of the New York Academy of Sciences Vol. 872, No. 1 ( 1999-04), p. 265-273
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 872, No. 1 ( 1999-04), p. 265-273
    Abstract: A bstract : In order to study cell kinetics involved in long‐term hematopoiesis, we studied single sorted candidate hematopoietic stem cells (HSC) from fetal liver cultured in the presence of a mixture of stimulatory cytokines. After 8‐10 days in culture, the number of cells varied from less than a hundred to more than ten thousand cells. Single cells in slowly growing colonies were recloned upon reaching a 100‐200‐cell stage. Strikingly, the number of cells in subclones varied widely again. These results are indicative of asymmetric divisions in primitive hematopoietic cells in which the proliferative potential and cell cycle properties are unevenly distributed among daughter cells. The continuous generation of heterogeneity in cell cycle properties among the clonal progeny of HSC appears a relevant mechanism to maintain long‐term maintenance of hematopoiesis in vitro and in vivo.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    URL: Article
    DOI: 10.1111/nyas.1999.872.issue-1
    DOI: 10.1111/j.1749-6632.1999.tb08471.x
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 1999
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    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
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  • 2
    Online Resource
    Online Resource
    Telomere Fluorescence Measurements in Granulocytes and T Lymphocyte Subsets Point to a High Turnover of Hematopoietic Stem Cells and Memory T Cells in Early Childhood
    Rockefeller University Press ; 1999
    In:  The Journal of Experimental Medicine Vol. 190, No. 2 ( 1999-07-19), p. 157-168
    Details
    In: The Journal of Experimental Medicine, Rockefeller University Press, Vol. 190, No. 2 ( 1999-07-19), p. 157-168
    Abstract: To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.
    Type of Medium: Online Resource
    ISSN: 0022-1007 , 1540-9538
    URL: Article
    DOI: 10.1084/jem.190.2.157
    RVK:
    XA 10000
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 1999
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  • 3
    Online Resource
    Online Resource
    Expression of MUC-1 Epitopes on Normal Bone Marrow: Implications for the Detection of Micrometastatic Tumor Cells
    American Society of Clinical Oncology (ASCO) ; 1999
    In:  Journal of Clinical Oncology Vol. 17, No. 5 ( 1999-05), p. 1535-1535
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 17, No. 5 ( 1999-05), p. 1535-1535
    Abstract: PURPOSE: The expression of the carcinoma-associated mucin MUC-1 is thought to be restricted to epithelial cells and is used for micrometastatic tumor cell detection in patients with solid tumors, including those with breast cancer. Little is known, however, about the expression of MUC-1 epitopes in normal hematopoietic cells. MATERIALS AND METHODS: MUC-1 expression was analyzed by flow cytometry and immunocytology on bone marrow (BM) mononuclear cells and purified CD34 + cells from healthy volunteers, using different anti-MUC-1–specific monoclonal antibodies. In addition, Western blotting of MUC-1 proteins was performed. RESULTS: Surprisingly, 2% to 10% of normal human BM mononuclear cells expressed MUC-1, as defined by the anti–MUC-1 antibodies BM-2 (2E11), BM-7, 12H12, MAM-6, and HMFG-1. In contrast, two antibodies recognizing the BM-8 and the HMFG-2 epitopes of MUC-1 were not detected. MUC-1 + cells from normal BM consisted primarily of erythroblasts and normoblasts. In agreement with this, normal CD34 + cells cultured in vitro to differentiate into the erythroid lineage showed a strong MUC-1 expression on day 7 proerythroblasts. Western blotting of these cells confirmed that the reactive species is the known high molecular weight MUC-1 protein. CONCLUSION: Our data demonstrate that some MUC-1 epitopes are expressed on normal BM cells and particularly on cells of the erythroid lineage. Hence the application of anti–MUC-1 antibodies for disseminated tumor cell detection in BM or peripheral blood progenitor cells may provide false-positive results, and only carefully evaluated anti–MUC-1 antibodies (eg, HMFG-2) might be selected. Furthermore, MUC-1–targeted immunotherapy in cancer patients might be hampered by the suppression of erythropoiesis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1999.17.5.1535
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1999
    detail.hit.zdb_id: 2005181-5
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