Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells.
Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells.
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DOI：
10.1084/jem.20111490
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发表时间：
2011-12-19
期刊：
影响因子：
--
通讯作者：
de Haan G
中科院分区：
文献类型：
--
作者：
Dykstra B;Olthof S;Schreuder J;Ritsema M;de Haan G
如使用克隆测定所示，小鼠HSC群体随着年龄经历定量和定性变化，包括谱系分化、HSC池大小、骨髓归巢效率和自我更新。造血干细胞（HSC）群体随着年龄的增长而变化，但这在多大程度上是由HSC亚型的定性与定量变化引起的尚不清楚。利用克隆分析，在这项研究中，我们表明，老化的HSC室经历了定量和定性的变化。我们观察到随着年龄的增长，HSC池大小的可变增加，伴随着主要是骨髓偏向的HSC的积累，再生的成熟后代比年轻的骨髓偏向的HSC少得多，并表现出降低的自我更新活性，通过长期二次移植测量。使用长期移植试验测量，旧HSC的骨髓归巢效率降低了两倍，功能频率也降低了类似的降低。同样，与年轻的HSC相比，在长期基质细胞共培养中，老年HSC的接种效率降低了两倍，增殖反应显著延迟，但在悬浮培养中无法区分。我们发现，这些功能缺陷是大多数或所有老年HSC的特征，并不表示表达HSC标志物的细胞的非功能性子集。此外，我们证明了具有老年HSC功能特性的细胞可以通过延长的连续移植直接从年轻的HSC中产生，这与它们通过细胞衰老过程产生的可能性一致。
As shown using clonal assays, the mouse HSC population undergoes quantitative as well as qualitative changes with age, including lineage differentiation, HSC pool size, marrow-homing efficiency, and self-renewal. Hematopoietic stem cell (HSC) populations change with aging, but the extent to which this is caused by qualitative versus quantitative alterations in HSC subtypes is unclear. Using clonal assays, in this study we show that the aging HSC compartment undergoes both quantitative and qualitative changes. We observed a variable increase of HSC pool size with age, accompanied by the accumulation of predominantly myeloid-biased HSCs that regenerate substantially fewer mature progeny than young myeloid-biased HSCs and exhibit reduced self-renewal activity as measured by long-term secondary transplantation. Old HSCs had a twofold reduction in marrow-homing efficiency and a similar decrease in functional frequency as measured using long-term transplantation assays. Similarly, old HSCs had a twofold reduced seeding efficiency and a significantly delayed proliferative response compared with young HSCs in long-term stromal cell co-cultures but were indistinguishable in suspension cultures. We show that these functional defects are characteristics of most or all old HSCs and are not indicative of a nonfunctional subset of cells that express HSC markers. Furthermore, we demonstrate that cells with functional properties of old HSCs can be generated directly from young HSCs by extended serial transplantation, which is consistent with the possibility that they arise through a process of cellular aging.
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DOI：
10.1111/j.1749-6632.2003.tb03247.x
发表时间：
2003-01-01
期刊：
HEMATOPOIETIC STEM CELLS 2002: GENETICS AND FUNCTION
影响因子：
--
作者：
Kim, M;Moon, HM;Spangrude, GJ
通讯作者：
Spangrude, GJ
影响因子：
23.9
作者：
Dykstra, Brad;Kent, David;Eaves, Connie
通讯作者：
Eaves, Connie
DOI：
10.1083/jcb.201010131
发表时间：
2011-04-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Liu L;Rando TA
通讯作者：
Rando TA
影响因子：
64.8
作者：
Rossi, Derrick J.;Bryder, David;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
82.9
作者：
Morrison, SJ;Wandycz, AM;Weissman, IL
通讯作者：
Weissman, IL