Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA; Division of Stem Cell Therapy, Center for Stem Cell Biology and Regeneration Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA.
Cell Stem Cell. 2018 Apr 5;22(4):600-607.e4. doi: 10.1016/j.stem.2018.03.013.
Aging is linked to functional deterioration and hematological diseases. The hematopoietic system is maintained by hematopoietic stem cells (HSCs), and dysfunction within the HSC compartment is thought to be a key mechanism underlying age-related hematopoietic perturbations. Using single-cell transplantation assays with five blood-lineage analysis, we previously identified myeloid-restricted repopulating progenitors (MyRPs) within the phenotypic HSC compartment in young mice. Here, we determined the age-related functional changes to the HSC compartment using over 400 single-cell transplantation assays. Notably, MyRP frequency increased dramatically with age, while multipotent HSCs expanded modestly within the bone marrow. We also identified a subset of functional cells that were myeloid restricted in primary recipients but displayed multipotent (five blood-lineage) output in secondary recipients. We have termed this cell type latent-HSCs, which appear exclusive to the aged HSC compartment. These results question the traditional dogma of HSC aging and our current approaches to assay and define HSCs.
衰老是与功能恶化和血液疾病相关的。造血系统由造血干细胞（HSCs）维持，而 HSC 隔室中的功能障碍被认为是与年龄相关的造血扰动的关键机制。使用具有五个血液谱系分析的单细胞移植测定法，我们之前在年轻小鼠的表型 HSC 隔室中鉴定出了骨髓限制的再生成祖细胞（MyRPs）。在这里，我们使用超过 400 个单细胞移植测定法确定了与年龄相关的 HSC 隔室的功能变化。值得注意的是，MyRP 频率随着年龄的增长而急剧增加，而多能 HSCs 在骨髓中适度扩增。我们还鉴定出了一组在原发性受者中骨髓限制但在继发性受者中显示多能（五个血液谱系）输出的功能细胞。我们将这种细胞类型称为潜伏-HSCs，它似乎仅存在于老年 HSC 隔室中。这些结果对 HSC 衰老的传统观念以及我们目前用于测定和定义 HSCs 的方法提出了质疑。
