In vivo fate-tracing studies using the Scl stem cell enhancer:: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis
In vivo fate-tracing studies using the Scl stem cell enhancer:: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis
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DOI：
10.1182/blood-2004-08-3037
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发表时间：
2005-04-01
期刊：
影响因子：
20.3
通讯作者：
Begley, CG
中科院分区：
文献类型：
--
作者：
Göthert, JR;Gustin, SE;Begley, CG
小鼠胚胎和成体造血干细胞（HSC）之间的谱系关系的证据主要是间接的。为了直接研究这种关系，我们在转基因小鼠（HSC-SCL-Cre-ERT）中表达了在干细胞白血病（Scl）干细胞增强子控制下的他莫昔芬诱导型Cre-EFT重组酶。为了确定功能性，将HSC-SCL-Cre-ERT转基因小鼠与Cre报告基因小鼠交配。流式细胞术和移植研究显示，他莫昔芬依赖性重组发生在90%以上的成年长期HSC中，而成熟祖细胞群体中的靶向比例显着较低。此外，转基因能够在妊娠第10天和第11天不可逆地标记胚胎HSC。5个月后，这些细胞参与骨髓造血。为了研究HSC的从头生成是否在胚胎发生过程中完成，将HSC-SCL-Cre-ERT标记的胎肝细胞移植到成年受体中。引人注目的是，在移植的标记细胞的比例和在体内剩余的HSC隔室是没有不同的，这意味着没有进一步的HSC生成发生在晚期胎儿和新生儿的发展阶段。这些数据首次证明了小鼠中妊娠中期胚胎和成体HSC之间的直接谱系关系。此外，HSC-SCL-Cre-ERT小鼠将提供一种有价值的工具，以实现HSC的时间控制遗传操作。(c)2005年，美国血液学会。
Evidence for the lineage relationship between embryonic and adult hematopoietic stem cells (HSCs) in the mouse is primarily indirect. In order to study this relationship in a direct manner, we expressed the tamoxifen-inducible Cre-EFT recombinase under the control of the stem cell leukemia (Scl) stem-cell enhancer in transgenic mice (HSC-SCL-Cre-ERT). To determine functionality, HSC-SCL-Cre-ERT transgenics were bred with Cre reporter mice. Flow cytometric and transplantation studies revealed tamoxifen-dependent recombination occurring in more than 90% of adult long-term HSCs, whereas the targeted proportion within mature progenitor populations was significantly lower. Moreover, the transgene was able to irreversibly tag embryonic HSCs on days 10 and 11 of gestation. These cells contributed to bone marrow hematopoiesis 5 months later. In order to investigate whether the de novo HSC generation is completed during embryogenesis, HSC-SCL-Cre-ERT-marked fetal liver cells were transplanted into adult recipients. Strikingly, the proportion of marked cells within the transplanted and the in vivo-remaining HSC compartment was not different, implying that no further HSC generation occurred during late fetal and neonatal stages of development. These data demonstrate for the first time the direct lineage relationship between midgestation embryonic and adult HSCs in the mouse. Additionally, the HSC-SCL-Cre-ERT mice will provide a valuable tool to achieve temporally controlled genetic manipulation of HSCs. (c) 2005 by The American Society of Hematology.