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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
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Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age

机译:人骨髓造血干细胞的频率增加,并且随着年龄的增长而受到骨髓偏向

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摘要

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 immunopheno-typic 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.
机译:在人类造血系统中,衰老与骨髓细胞减少,免疫系统功能降低以及贫血和其他血液系统疾病和恶性肿瘤的发生有关。小鼠的最新研究表明,衰老过程中造血干细胞(HSC)群体内的变化显着促进了这些与年龄相关的造血病理的表现。尽管已显示小鼠HSC群体会随着年龄的变化而在数量和功能上发生变化,但人类HSC和祖细胞群体在衰老过程中的变化尚未得到充分表征。为了阐明可能易与年龄相关的造血功能障碍的老年人类造血系统的特性,我们评估了健康,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。我们发现,与年轻的HSC相比,老年免疫表型人HSC的频率增加,静止性更小,并且显示出偏向于骨髓的分化潜能。基因表达谱分析表明,老年免疫表型人类HSC转录上调与细胞周期,髓系谱系和髓系恶性肿瘤相关的基因。人类HSC的这些与年龄相关的频率,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,表明造血老化是进化上保守的过程。

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