Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin
Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin
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DOI：
10.1073/pnas.0402270102
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发表时间：
2005-01-04
影响因子：
11.1
通讯作者：
Cumano, A
中科院分区：
文献类型：
--
作者：
Bertrand, JY;Giroux, S;Cumano, A
人们对中胚层发育的造血干细胞(HSC)知之甚少。为了获得更多关于胚胎内HSC起源位置的信息，我们从小鼠的主动脉-性腺-中肾(AGM)中纯化了多潜能造血祖细胞。这一群体表达c-Kit、AA4.1、CD31和CD41，但不表达Flk1，主要为CD45阴性，被证明能够在亚致死剂量Rag2Gammac(-/-)受者中进行长期重建。我们将GATA-2、GATA-3和Imo2的表达归于AGM-HSC，而红系祖细胞只表达GATA-2。这种独特的表面标志物和转录因子的组合可以在AGM中分配给主动脉内膜簇和主动脉内皮细胞下的主动脉下斑块。综上所述，这些数据表明胚胎HSCs与胎肝和成体HSCs的不同之处在于CD45的低表达，(I)它并不像以前认为的那样与主动脉内皮细胞共存，(Iii)在性交后10.5天，定位于主动脉内皮细胞下面的内脏中胚层，在GATA-3(+)CD31(+)细胞团中。
Little is known about hematopoietic stem cell (HSC) development from mesoderm. To gain more information on the intraembryonic HSC site of origin, we purified multipotent hematopoietic progenitors from the aorta-gonads-mesonephros (AGM) of mice. This population, expressing c-Kit, AA4.1, CD31, and CD41, but not Flk1, and mainly negative for CD45, proved capable of long-term reconstitution in sublethally irradiated Rag2gammac(-/-) recipients. We assigned the expression of GATA-2, GATA-3, and Imo2 to AGM-HSC, whereas erythromyeloid progenitors express only GATA-2. This unique combination of surface markers and transcription factors could be allocated in the AGM to the intraaortic clusters and the subaortic patches underlying aortic endothelial cells. Taken together, those data indicate that embryonic HSCs (i) differ from their fetal liver and adult counterpart by the low expression of CD45, (it) do not colocalize with aortic endothelial cells as previously thought, and (iii) are localized, at 10.5 days postcoitum, in the splanchnic mesoderm underlying aortic endothelial cells, within GATA-3(+)CD31(+) cell clusters.