Age-associated characteristics of murine hematopoietic stem cells.
Age-associated characteristics of murine hematopoietic stem cells.
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DOI：
10.1084/jem.192.9.1273
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发表时间：
2000-11-06
影响因子：
15.3
通讯作者：
Nakauchi, H
中科院分区：
文献类型：
--
作者：
Sudo, K;Ema, H;Morita, Y;Nakauchi, H
人们对造血干细胞（HSCs）与年龄相关的功能变化知之甚少。我们通过从C57BL/6小鼠的骨髓中分离CD34⁻/lowc - Kit⁺Sca - 1⁺谱系标记阴性（CD34⁻KSL）细胞，在克隆水平上研究衰老的HSCs。随着年龄的增长，CD34⁻KSL细胞群逐渐扩大。无论年龄大小，这些细胞在有干细胞因子和白细胞介素（IL）-3的情况下可在体外形成集落，但单独有IL - 3时则不能。它们不能形成第12天的脾集落形成单位（CFU - S），这表明它们是具有髓系分化潜能的原始细胞。体内极限稀释实验表明，在CD34⁻KSL细胞群以及未分离的骨髓细胞中，多谱系再增殖细胞的数量从2月龄到18月龄增加了两倍。此外，我们在18月龄小鼠的CD34⁻KSL细胞中检测到另一个不同于HSCs的再增殖细胞群。这些再增殖细胞向淋巴细胞分化的潜能较低，但如二次移植所表明的，保留了自我更新潜能。我们提出，由于HSCs的反复自我更新，随着年龄的增长，HSCs逐渐积累，同时伴有淋巴细胞分化潜能较低的细胞。
Little is known of age-associated functional changes in hematopoietic stem cells (HSCs). We studied aging HSCs at the clonal level by isolating CD34−/lowc-Kit+Sca-1+ lineage marker–negative (CD34−KSL) cells from the bone marrow of C57BL/6 mice. A population of CD34−KSL cells gradually expanded as age increased. Regardless of age, these cells formed in vitro colonies with stem cell factor and interleukin (IL)-3 but not with IL-3 alone. They did not form day 12 colony-forming unit (CFU)-S, indicating that they are primitive cells with myeloid differentiation potential. An in vivo limiting dilution assay revealed that numbers of multilineage repopulating cells increased twofold from 2 to 18 mo of age within a population of CD34−KSL cells as well as among unseparated bone marrow cells. In addition, we detected another compartment of repopulating cells, which differed from HSCs, among CD34−KSL cells of 18-mo-old mice. These repopulating cells showed less differentiation potential toward lymphoid cells but retained self-renewal potential, as suggested by secondary transplantation. We propose that HSCs gradually accumulate with age, accompanied by cells with less lymphoid differentiation potential, as a result of repeated self-renewal of HSCs.