Development and aging of primitive hematopoietic stem cells in BALB cBy mice

Development and aging of primitive hematopoietic stem cells in BALB cBy mice
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DOI:
10.1016/s0301-472x(99)00018-1
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发表时间:
1999-05-01
影响因子:
2.6
通讯作者:
Harrison, DE
Harrison, DE
中科院分区:
医学4区
文献类型:
--
作者:
Chen, JC;Astle, CM;Harrison, DE

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评估单个造血干细胞(HSC)的功能是一个困难且重要的问题,使用新的竞争稀释测定法对体内细胞的破坏最小而对细胞的破坏进行了测量,每个fiSC的功能能力以及HSC浓度。基于泊松概率对HSC分布在接受者中。假设供体贡献的预测假设供体HSC功能能力和浓度不同的前面模型与实际观察结果进行了比较。接受预测和观察之间差异最小的模型被接受。在BALB/CBY(BALB)小鼠中,假设来自同一供体的HSC相等功能能力的模型非常适合实际观察结果,这表明所有HSC在开发或衰老过程中的任何特定时间点上都是功能均匀的。每个细胞的相对HSC功能能力在发育过程中降低,因此胎儿HSC具有年轻成人HSC功能能力的1.6至3.0倍。下降随着年龄的增长而下降,因此年轻的HSC具有旧HSC的功能能力的1.6至2.0倍,植入和功能的HSC浓度在16天的胎儿肝细胞和骨髓细胞(BMC)中相似。 - 月和25至28个月大的成年小鼠。在Bale或CBYD6F1受体中测试时,它们为10或4 HSC,所有HSC都是多能的,并产生淋巴样和髓样后代(r = 0.80至0.80至0.80至0.98,p <0.01),两种类型的HSC,两种类型长期维持克隆稳定性的受体,因此6和9个月时供体细胞的百分比密切相关(r = 0.72至0.93,p <0.01),尽管Bale接受者老年供体的HSC保持克隆稳定性,但同一年龄供体的HSC未能显示出CBYB6F1接收者的克隆稳定性,也许是由于较不合适的宿主环境,而所有HSC的HSC来自Bale小鼠的所有HSC。在给定的生活阶段似乎具有同等的功能水平,并且通过发展和衰老逐渐疲惫。 (C)1999年国际实验血液学学会。由Elsevier Science Inc.出版
Evaluating the function of an individual hematopoietic stem cell (HSC) is a difficult and important problem, The functional ability per FISC, as well as the HSC concentration, was measured with minimal disruption to the cells in vivo using the new competitive dilution assay. Distribution of HSC into recipients was modeled based on Poisson probabilities. Predictions of donor contributions front models assuming different levels of donor HSC functional ability and concentration were compared to actual observations. The model with the least difference between predictions and observations was accepted. In BALB/cBy (BALB) mice, models assuming equal functional ability of HSC from the same donor fit extremely well with actual observations, suggesting that all HSC are functionally homogeneous at any particular time point during development or aging. Relative HSC functional ability per cell declined during development, so that a fetal HSC had 1.6 to 3.0 times the functional ability of a young adult HSC. The decline continued with age, so that a young adult HSC had 1.6 to 2.0 times the functional ability of an old HSC, Concentrations of HSC that engrafted and functioned were similar among 16-day fetal liver cells and bone marrow cells (BMC) from 3-month and 25 to 28-month-old adult mice. They were either 10 or 4 HSC per million cells when tested in BALE or CByD6F1 recipients, respectively, All HSC were pluripotent and produced lymphoid and myeloid descendants proportionally (r = 0.80 to 0.98, p < 0.01), Fetal and young HSC in both types of recipients maintained clonal stability long term so that percentages of donor cells at 6 and 9 months were strongly correlated (r = 0.72 to 0.93, p < 0.01), Although HSC from aged donors in BALE recipients maintained clonal stability, HSC from the same aged donors failed to show clonal stability in CByB6F1 recipients, perhaps due to the less suitable host environment, All HSC from BALE mice seemed to have equal functional levels at a given stage of life and were gradually exhausted simultaneously through development and aging. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.