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      Intermediate-term hematopoietic stem cells with extended but time-limited reconstitution potential.

      Cell Stem Cell

      genetics, Animals, fms-Like Tyrosine Kinase 3, Time Factors, Receptors, Cell Surface, Mice, Inbred C57BL, Mice, Integrin alpha2, metabolism, cytology, Hematopoietic Stem Cells, Gene Expression Regulation, Gene Expression Profiling, Cells, Cultured, Cell Separation, Cell Lineage, Cell Division, Cell Differentiation, Antigens, CD34, Antigens, CD

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          Abstract

          Sustained blood cell production depends on divisions by hematopoietic stem cells (HSCs) that yield both differentiating progeny as well as new HSCs via self-renewal. Differentiating progeny remain capable of self-renewal, but only HSCs sustain self-renewal through successive divisions securely enough to maintain clones that persist life-long. Until recently, the first identified next stage consisted of "short-term" reconstituting cells able to sustain clones of differentiating cells for only 4-6 weeks. Here we expand evidence for a numerically dominant "intermediate-term" multipotent HSC stage in mice whose clones persist for 6-8 months before becoming extinct and that are separable from both short-term as well as permanently reconstituting "long-term" HSCs. The findings suggest that the first step in stem cell differentiation consists not in loss of initial capacity for serial self-renewal divisions, but rather in loss of mechanisms that stabilize self-renewing behavior throughout successive future stem cell divisions. Copyright 2010 Elsevier Inc. All rights reserved.

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          Journal
          10.1016/j.stem.2009.11.014
          20074534

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