A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells
A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells
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DOI：
10.1182/blood-2007-11-123547
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发表时间：
2008-06-15
期刊：
影响因子：
20.3
通讯作者：
Muller-Sieburg, Christa E.
中科院分区：
文献类型：
--
作者：
Cho, Rebecca H.;Sieburg, Hans B.;Muller-Sieburg, Christa E.
造血干细胞（hsc）是否随年龄变化一直存在争议。先前，我们发现年轻小鼠的HSC室由不同的亚群组成，每个亚群都具有预定的自我更新和分化行为。根据造血干细胞的分化程序，可将其分为三类：淋巴细胞偏倚、平衡型和髓细胞偏倚。我们现在表明，衰老导致这些HSC子集的表现发生显著变化。对再生造血干细胞的克隆分析表明，淋巴细胞偏向性造血干细胞丢失，而长寿的骨髓偏向性造血干细胞在老年人中积累。在所有测试中，来自年轻和年老来源的髓细胞偏倚hsc的表现相似。这表明衰老不会改变单个hsc。相反，衰老改变了HSC细胞室的克隆组成。我们进一步表明遗传因素有助于HSC亚群的年龄相关变化。与B6小鼠相比，老年D2小鼠向骨髓偏向性hsc的转变更为明显，T细胞和b细胞前体的数量相应减少。这表明血液中淋巴细胞水平低可能是HSC老化的标志。淋巴细胞偏向性造血干细胞的缺失可能导致老年人对传染病和癌症的免疫反应受损。
Whether hematopoietic stem cells (HSCs) change with aging has been controversial. Previously, we showed that the HSC compartment in young mice consists of distinct subsets, each with predetermined self-renewal and differentiation behavior. Three classes of HSCs can be distinguished based on their differentiation programs: lymphoid biased, balanced, and myeloid biased. We now show that aging causes a marked shift in the representation of these HSC subsets. A clonal analysis of repopulating HSCs demonstrates that lymphoid-biased HSCs are lost and long-lived myeloid-biased HSCs accumulate in the aged. Myelold-biased HSCs from young and aged sources behave similarly in all aspects tested. This indicates that aging does not change individual HSCs. Rather, aging changes the clonal composition of the HSC compartment. We show further that genetic factors contribute to the age-related changes of the HSC subsets. In comparison with B6 mice, aged D2 mice show a more pronounced shift toward myeloid-biased HSCs with a corresponding reduction in the number of both T- and B-cell precursors. This suggests that low levels of lymphocytes in the blood can be a marker for HSC aging. The loss of lymphoid-biased HSCs may contribute to the impaired immune response to infectious diseases and cancers in the aged.