Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver
Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver
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DOI：
10.1182/blood.v96.12.3757.h8003757_3757_3762
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发表时间：
2000-12-01
期刊：
影响因子：
20.3
通讯作者：
Nakauchi, H
中科院分区：
文献类型：
--
作者：
Hsu, HC;Ema, H;Nakauchi, H
在小鼠胚胎发育过程中，内皮细胞和造血细胞中表达的Tie-2受体酪氨酸激酶被认为在血管生成和造血过程中发挥作用。本文探讨了Tie-2在孕14天胎肝造血干细胞(HSCs)上的表达。使用抗Tie-2单抗，在Kit阳性、SCA-1阳性、谱系阴性或低以及AA4.1阳性(KSLA)的HSC群体中，大约7%的HSC群体中检测到Tie-2的表达。这些Tie-2阳性的KSLA(T+KSLA)细胞占胎肝细胞的0.01%~0.02%。对T+KSLA细胞和Tie-2阴性KSLA(T-KSLA)细胞进行了体外克隆和体内竞争再扩增实验，在干细胞因子、白介素3和促红细胞生成素存在的情况下，T+KSLA细胞在体外形成集落的比例为80%，而T-KSLA细胞的比例为40%。在T+KSLA细胞中检测到长期多系再增殖细胞，而在T-KSLA细胞中未检测到。活体极限稀释分析表明，8个T+KSLA细胞中至少有1个是这样的再增殖细胞。有限数量的T+KSLA细胞二次移植的成功表明这些细胞具有自我更新的潜力，此外，T+KSLA细胞在条件新生小鼠体内的植入表明这些HSCs可以平等地适应成人和新生儿的造血环境。这些数据表明，T+KSLA细胞代表小鼠胎肝中的HSCs。(C)2000年，由美国血液病学会提供。
Tie-2 receptor tyrosine kinase expressed in endothelial and hematopoietic cells is believed to play a role in both angiogenesis and hematopoietic during development of the mouse embryo. This article addressed whether Tie-2 is expressed on fetal liver hematopoietic stem cells (HSCs) at day 14 of gestation. With the use of anti-Tie-2 monoclonal antibody, its expression was detected in approximately 7% of an HSC population of Kit-positive, Sca-1-positive, lineage-negative or -low, and AA4.1-positive (KSLA) cells. These Tie-2-positive KSLA (T+ KSLA) cells rep resent 0.01% to 0.02% of fetal liver cells. In vitro colony and in vivo competitive repopulation assays were performed for T+ KSLA cells and Tie-2-negative KSLA (T- KSLA) cells, In the presence of stem cell factor, interleukin-3, and erythropoietin, 80% of T+ KSLA cells formed colonies in vitro, compared with 40% of T- KSLA cells. Long-term multilineage repopulating cells were detected in T+ KSLA cells, but not in T- KSLA cells. An in vive limiting dilution analysis revealed that at least 1 of 8 T+ KSLA cells were such repopulating cells. The successful secondary transplantation initiated with a limited number of T+ KSLA cells suggests that these cells have self-renewal potential, In addition, engraftment of T+ KSLA cells in conditioned newborn mice indicates that these HSCs can be adapted equally by the adult and newborn hematopoietic environments. The data suggest that T+ KSLA cells represent HSCs in the murine fetal liver. (C) 2000 by The American Society of Hematology.