Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment.
Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment.
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DOI：
10.1016/j.stem.2018.03.013
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发表时间：
2018-04-05
期刊：
影响因子：
23.9
通讯作者：
Nakauchi H
中科院分区：
文献类型：
--
作者：
Yamamoto R;Wilkinson AC;Ooehara J;Lan X;Lai CY;Nakauchi Y;Pritchard JK;Nakauchi H
衰老与功能退化和血液病有关。造血系统由造血干细胞（HSC）维持，HSC区室内的功能障碍被认为是年龄相关造血扰动的关键机制。使用单细胞移植试验与五个血液谱系分析，我们以前确定了骨髓限制性再生祖细胞（MyRPs）内的表型HSC车厢在年轻的小鼠。在这里，我们使用400多个单细胞移植试验确定了HSC区室的年龄相关功能变化。值得注意的是，MyRP频率随着年龄的增长而显着增加，而多能造血干细胞在骨髓中适度扩增。我们还确定了一个子集的功能性细胞，骨髓限制在初级受体，但显示多能（五血系）输出在二级受体。我们将这种细胞类型称为潜伏HSC，其似乎专属于老年HSC隔室。这些结果质疑了HSC老化的传统教条和我们目前测定和定义HSC的方法。单细胞移植揭示了HSC组成中与年龄相关的显著变化，MyRP/MySC随着年龄的增长而增加，因为整个BM细胞和HSC区室的频率。通过使用单细胞移植的大规模克隆分析，探索HSC功能的年龄相关变化。他们发现骨髓限制性再生祖细胞（MyRPs）大量增加，以及仅在二次移植中显示更广泛分化能力的MyRPs群体，这表明有助于造血衰老的其他机制。
Aging is linked to functional deterioration and hematological diseases. The hematopoietic system is maintained by hematopoietic stem cells (HSCs), and dysfunction within the HSC compartment is thought to be a key mechanism underlying age-related hematopoietic perturbations. Using single-cell transplantation assays with five blood-lineage analysis, we previously identified myeloid-restricted repopulating progenitors (MyRPs) within the phenotypic HSC compartment in young mice. Here, we determined the age-related functional changes to the HSC compartment using over 400 single-cell transplantation assays. Notably, MyRP frequency increased dramatically with age, while multipotent HSCs expanded modestly within the bone marrow. We also identified a subset of functional cells that were myeloid restricted in primary recipients but displayed multipotent (five blood-lineage) output in secondary recipients. We have termed this cell type latent-HSCs, which appear exclusive to the aged HSC compartment. These results question the traditional dogma of HSC aging and our current approaches to assay and define HSCs. Single-cell transplantation reveals dramatic age-related changes in HSC composition MyRPs/MySCs increase with age as a frequency of whole BM cells and the HSC compartment Latent-HSCs were identified exclusively in the aged bone marrow Latent-HSCs have restricted potential in primary, but not secondary, transplants Yamamoto et al. explore age-related changes to HSC function through large-scale clonal analysis using single-cell transplantation. They find large increases in myeloid-restricted repopulating progenitors (MyRPs) as well as a population of MyRPs that display a broader differentiation capacity only in secondary transplants, suggesting additional mechanisms contributing to hematopoietic aging.
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影响因子：
64.8
作者：
Rodriguez-Fraticelli AE;Wolock SL;Weinreb CS;Panero R;Patel SH;Jankovic M;Sun J;Calogero RA;Klein AM;Camargo FD
通讯作者：
Camargo FD
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
64.5
作者：
Bernitz, Jeffrey M.;Kim, Huen Suk;MacArthur, Ben;Sieburg, Hans;Moore, Kateri
通讯作者：
Moore, Kateri
影响因子：
16.6
作者：
Grover A;Sanjuan-Pla A;Thongjuea S;Carrelha J;Giustacchini A;Gambardella A;Macaulay I;Mancini E;Luis TC;Mead A;Jacobsen SE;Nerlov C
通讯作者：
Nerlov C
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ