The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice.
The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice.
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DOI：
10.1182/blood-2008-07-167106
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发表时间：
2009-03
期刊：
影响因子：
20.3
通讯作者：
T. Yokota;K. Oritani;S. Butz;K. Kokame;P. Kincade;T. Miyata;D. Vestweber;Y. Kanakura
中科院分区：
文献类型：
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作者：
T. Yokota;K. Oritani;S. Butz;K. Kokame;P. Kincade;T. Miyata;D. Vestweber;Y. Kanakura
虽然最近的进展已经使造血干细胞（HSC）富集到接近纯度，但更多关于其特征的信息将提高我们对其发育和阶段相关功能的理解。在这里，使用微阵列技术，我们确定了内皮细胞选择性粘附分子（ESAM）作为一种新的标记，小鼠胎肝HSC。Esam在富含Rag 1（-）c-kit（Hi）Sca 1（+）HSC的组分中以高水平表达，但随着Rag 1位点的激活而急剧下调，Rag 1位点是E14.5肝脏中最原始淋巴祖细胞的有效标记。HSC富集组分可根据ESAM水平分为2个组分。在造血祖细胞内皮细胞抗原中，ESAM表达与HSC活性密切相关。ESAM（Hi）人群高度富集多能骨髓-红系祖细胞和具有淋巴细胞生成活性的原始祖细胞，并在致死性照射受体中专门重建长期淋巴细胞生成。在E9.5-10.5性腺中肾区的Tie 2（+）c-kit（+）淋巴造血细胞也表达高水平的ESAM。此外，ESAM在成人骨髓中的原始造血祖细胞上被检测到。有趣的是，ESAM在HSC富集组分中的表达在老年小鼠中上调。我们的结论是ESAM标志着小鼠胎肝中的HSC，并将促进整个生命的造血研究。
Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified endothelial cell-selective adhesion molecule (ESAM) as a novel marker for murine HSCs in fetal liver. Esam was expressed at high levels within a Rag1(-) c-kit(Hi) Sca1(+) HSC-enriched fraction, but sharply down-regulated with activation of the Rag1 locus, a valid marker for the most primitive lymphoid progenitors in E14.5 liver. The HSC-enriched fraction could be subdivided into 2 on the basis of ESAM levels. Among endothelial antigens on hematopoietic progenitors, ESAM expression showed intimate correlation with HSC activity. The ESAM(Hi) population was highly enriched for multipotent myeloid-erythroid progenitors and primitive progenitors with lymphopoietic activity, and exclusively reconstituted long-term lymphohematopoiesis in lethally irradiated recipients. Tie2(+) c-kit(+) lymphohematopoietic cells in the E9.5-10.5 aorta-gonad-mesonephros region also expressed high levels of ESAM. Furthermore, ESAM was detected on primitive hematopoietic progenitors in adult bone marrow. Interestingly, ESAM expression in the HSC-enriched fraction was up-regulated in aged mice. We conclude that ESAM marks HSC in murine fetal liver and will facilitate studies of hematopoiesis throughout life.