The positive regulatory effect of TGF-β2 on primitive murine hemopoietic stem and progenitor cells is dependent on age, genetic background, and serum factors
The positive regulatory effect of TGF-β2 on primitive murine hemopoietic stem and progenitor cells is dependent on age, genetic background, and serum factors
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DOI：
10.4049/jimmunol.173.4.2486
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发表时间：
2004-08-15
影响因子：
4.4
通讯作者：
Snoeck, HW
中科院分区：
文献类型：
--
作者：
Henckaerts, E;Langer, JC;Snoeck, HW
tgf - β被认为是造血干细胞和祖细胞的负调节因子。我们之前已经证明，tgf - β亚型tgf - β 2实际上是体内小鼠造血干细胞功能的正调节因子。在体外实验中，tgf - β 2对纯化的lin-Sca1(++)kit(+) （LSK）细胞的增殖具有双相剂量效应，tgf - β 1和tgf - β 3对LSK细胞的增殖具有低浓度的刺激作用，且存在小鼠品系依赖性变化。在这项研究中，我们报道了tgf - β 2对C57BL/6小鼠LSK细胞增殖的刺激作用随着年龄和复制应激的增加而增加，而在DBA/2小鼠中则没有。BXD重组菌株tgf - β 2效应的年龄相关变化与寿命相关。tgf - β 2对LSK细胞增殖的刺激作用需要一种或多种存在于胎牛和小鼠血清中的非蛋白、低分子量因子。该因子在小鼠血清中的活性随着年龄的增长而增加。综上所述，我们的数据表明，tgf - β 2和尚不清楚的血清因子在造血干细胞区室衰老中发挥了作用，也可能在机体衰老中发挥了作用。
TGF-beta is considered a negative regulator of hemopoietic stem and progenitor cells. We have previously shown that one TGF-beta isoform, TGF-beta2, is, in fact, a positive regulator of murine hemopoietic stem cell function in vivo. In vitro, TGF-beta2, but not TGF-beta1 and TGF-beta3, had a biphasic dose response on the proliferation of purified lin-Sca1(++)kit(+) (LSK) cells, with a stimulatory effect at low concentrations, which was subject to mouse strain-dependent variation. In this study we report that the stimulatory effect of TGF-beta2 on the proliferation of LSK cells increases with age and after replicative stress in C57BL/6, but not in DBA/2, mice. The age-related changes in the TGF-beta2 effect correlated with life span in BXD recombinant strains. The stimulatory effect of TGF-beta2 on the proliferation of LSK cells requires one or more nonprotein, low m.w. factors present in fetal calf and mouse sera. The activity of this factor(s) in mouse serum increases with age. Taken together, our data suggest a role for TGF-beta2 and as yet unknown serum factors in the aging of the hemopoietic stem cell compartment and possibly in organismal aging.