在稳态下的分部历史和造血干细胞功能。
Divisional history and hematopoietic stem cell function during homeostasis.
机构信息
Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA ; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA ; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA ; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
出版信息
Stem Cell Reports. 2014 Mar 20;2(4):473-90. doi: 10.1016/j.stemcr.2014.01.016. eCollection 2014 Apr 8.
We investigated the homeostatic behavior of hematopoietic stem and progenitor cells (HSPCs) temporally defined according to their divisional histories using an HSPC-specific GFP label-retaining system. We show that homeostatic hematopoietic stem cells (HSCs) lose repopulating potential after limited cell divisions. Once HSCs exit dormancy and accrue divisions, they also progressively lose the ability to return to G0 and functional activities associated with quiescent HSCs. In addition, dormant HSPCs phenotypically defined as multipotent progenitor cells display robust stem cell activity upon transplantation, suggesting that temporal quiescence is a greater indicator of function than cell-surface phenotype. Our studies suggest that once homeostatic HSCs leave dormancy, they are slated for extinction. They self-renew phenotypically, but they lose self-renewal activity. As such, they question self-renewal as a characteristic of homeostatic, nonperturbed HSCs in contrast to self-renewal demonstrated under stress conditions.
我们使用一种造血干细胞（HSPC）特异性 GFP 标记保留系统，根据其分裂历史对造血干细胞和祖细胞（HSPCs）进行时间定义，研究其体内平衡行为。我们发现，具有体内平衡作用的造血干细胞（HSCs）在有限的细胞分裂后会丧失再生潜能。一旦 HSCs 从休眠中苏醒并开始分裂，它们也逐渐丧失回到 G0 状态的能力以及与静止 HSCs 相关的功能活性。此外，在移植过程中，处于休眠状态的多能祖细胞表型定义的 HSPCs 表现出强大的干细胞活性，这表明暂时静止是功能的一个更好指标，而不是细胞表面表型。我们的研究表明，一旦体内平衡的 HSCs 离开休眠状态，它们就注定要灭绝。它们在表型上自我更新，但丧失自我更新活性。因此，它们质疑自我更新是体内平衡、未受干扰的 HSCs 的特征，与在应激条件下表现出的自我更新形成对比。
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