Ontario Cancer Institute, Toronto, ON M5G 2M9, Canada.
Cell Stem Cell. 2010 Jan 8;6(1):48-58. doi: 10.1016/j.stem.2009.11.014.
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.
持续的血细胞生成依赖于造血干细胞（HSCs）的分裂，这些细胞通过自我更新产生分化的后代和新的 HSCs。分化的后代仍然具有自我更新的能力，但只有 HSCs 通过连续的分裂来维持自我更新，以确保能够长期维持克隆。直到最近，第一个被确定的下一个阶段包括“短期”重建细胞，这些细胞只能维持分化细胞的克隆 4-6 周。在这里，我们扩展了在小鼠中存在数量占优势的“中期”多能 HSC 阶段的证据，其克隆在灭绝之前可以持续 6-8 个月，并且可以与短期以及永久性重建的“长期”HSCs 分离。这些发现表明，干细胞分化的第一步不是丧失最初的连续自我更新分裂能力，而是丧失了在连续的未来干细胞分裂过程中稳定自我更新行为的机制。
