Age-associated changes in the differentiation potentials of human circulating hematopoietic progenitors to T- or NK-lineage cells.
Age-associated changes in the differentiation potentials of human circulating hematopoietic progenitors to T- or NK-lineage cells.
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DOI：
10.4049/jimmunol.1203189
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发表时间：
2013-06-15
期刊：
影响因子：
--
通讯作者：
Kusunoki Y
中科院分区：
文献类型：
--
作者：
Kyoizumi S;Kubo Y;Kajimura J;Yoshida K;Imai K;Hayashi T;Nakachi K;Young LF;Moore MA;van den Brink MR;Kusunoki Y
人类造血干细胞的T细胞和NK细胞（T/NK）潜能的变化是未知的。在这里，我们通过有限稀释试验，使用与表达Notch 1配体Delta样1的OP 9-DL 1基质细胞共培养，对正常成人外周血（PB）中循环的CD 34阳性/谱系标记阴性（CD 34 +Lin−）细胞群中的T/NK前体细胞进行计数和表征。发现CD 34 +Lin−细胞中T细胞前体的频率随着供体年龄的增加而降低，而NK细胞与T细胞前体频率的比率（NK/T比率）随着年龄的增加而增加，这表明PB祖细胞的淋巴分化潜力随着年龄的增长从T细胞谱系转移到NK细胞谱系。CD 34 +Lin−细胞的克隆分析表明，NK/T比值的差异归因于单系和双系T/NK前体克隆的不同分布。由于几乎所有的克隆在与0 P9-DL 1细胞共培养中保留单核细胞和/或粒细胞分化潜能，因此认为PB中的T/NK前体细胞包含在T/NK/骨髓多能祖细胞的库中。年龄相关的NK细胞相对于T细胞定型的增加可能发生在具有T/NK/髓系潜能的前体细胞中。
Age-associated changes of T- and NK-cell (T/NK) potential of human hematopoietic stem cells are unknown. Here, we enumerate and characterize T/NK precursors among CD34-positive/lineage marker-negative (CD34+Lin−) cell populations circulating in normal human adult peripheral blood (PB) by a limiting-dilution assay using co-culture with OP9-DL1 stroma cells expressing Notch 1 ligand, Delta-like 1. The frequency of T-cell precursors in CD34+Lin− cells was found to decrease with donor age, while the ratio of NK- to T-cell precursor frequency (NK/T ratio) increased with age, suggesting that lymphoid differentiation potential of PB progenitors shifts from T- to NK-cell lineage with aging. Clonal analyses of CD34+Lin− cells showed that differences in the NK/T ratio were attributable to different distributions of single- and dual-lineage T/NK precursor clones. Since nearly all of the clones retained monocyte and/or granulocyte differentiation potentials in co-culture with OP9-DL1 cells, T/NK precursors in PB are considered to be contained in the pool of T/NK/myeloid multi-potent progenitors. The age-associated increase in NK- over T-cell commitment might occur in precursor cells with T/NK/myeloid potential.
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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：
3.9
作者：
Borrego, F;Alonso, MC;Solana, R
通讯作者：
Solana, R
影响因子：
20.3
作者：
De Obaldia, Maria Elena;Bell, J. Jeremiah;Bhandoola, Avinash
通讯作者：
Bhandoola, Avinash
影响因子：
16.8
作者：
Panda A;Arjona A;Sapey E;Bai F;Fikrig E;Montgomery RR;Lord JM;Shaw AC
通讯作者：
Shaw AC
影响因子：
20.3
作者：
La Motte-Mohs, RN;Herer, E;Zúñiga-Pflücker, JC
通讯作者：
Zúñiga-Pflücker, JC