Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
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DOI：
10.1073/pnas.1116110108
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发表时间：
2011-12-13
影响因子：
11.1
通讯作者：
Weissman, Irving L.
中科院分区：
文献类型：
--
作者：
Pang, Wendy W.;Price, Elizabeth A.;Weissman, Irving L.
在人类造血系统中，衰老与骨髓细胞减少、适应性免疫系统功能下降以及贫血和其他血液学疾病和恶性肿瘤的发病率增加有关。最近在小鼠中的研究表明，在衰老期间造血干细胞（HSC）群体内的变化对这些与年龄相关的造血病理的表现有显着贡献。虽然小鼠HSC群体已被证明随着年龄的增长在数量和功能上都发生了变化，但人类HSC和祖细胞群体在衰老过程中的变化还没有完全表征。为了阐明老年人造血系统可能易患与年龄相关的造血功能障碍的特性，我们评估了来自健康、血液学正常的年轻人和老年人骨髓样本的免疫表型HSC和其他造血祖细胞群体。我们发现，老年免疫表型的人HSC的频率增加，是不太静止，并表现出骨髓偏向分化潜力相比，年轻的HSC。基因表达谱分析显示，老年免疫表型的人HSC转录上调与细胞周期，髓系特异性和髓系恶性肿瘤相关的基因。这些与年龄相关的人类HSC的频率、发育潜力和基因表达谱的变化与在小鼠HSC中观察到的变化相似，表明造血衰老是一个进化保守的过程。
In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.