EPCR expression marks UM171-expanded CD34+ cord blood stem cells

EPCR expression marks UM171-expanded CD34+ cord blood stem cells
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DOI:
10.1182/blood-2016-11-750729
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发表时间:
2017-06-22
期刊:
影响因子:
20.3
通讯作者:
Sauvageau, Guy
Sauvageau, Guy
中科院分区:
医学1区
文献类型:
--
作者:
Fares, Iman;Chagraoui, Jalila;Sauvageau, Guy

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当暴露于造血干细胞(HSC)自我更新激动剂UM 171时,一小部分人脐带血CD 34(+)细胞表达内皮蛋白C受体(EPCR/CD 201/PROCR)。在这篇文章中,我们表明,EPCR阳性的UM 171处理的细胞,而不是EPCR阴性的细胞,表现出强大的多谱系再增殖和免疫功能低下的小鼠系列重建能力。与其他干细胞标志物如CD 38相反,当细胞被引入培养物中时,EPCR表达得以维持,而与UM 171处理无关。尽管EPCR的工程化过表达不能再现UM 171对HSC活性的影响,但其表达是人HSC的重建活性所需的。总之,我们的研究结果表明,EPCR是一个可靠的和细胞培养相容的标志物UM 171扩增的人脐带血造血干细胞。
A small subset of human cord blood CD34(+) cells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem cell (HSC) self-renewal agonist UM171. In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage repopulation and serial reconstitution ability in immunocompromised mice. In contrast to other stem cell markers, such as CD38, EPCR expression is maintained when cells are introduced in culture, irrespective of UM171 treatment. Although engineered overexpression of EPCR fails to reproduce the effects of UM171 on HSC activity, its expression is required for the repopulating activity of human HSCs. Altogether, our results indicate that EPCR is a reliable and cell culture-compatible marker of UM171-expanded human cord blood HSCs.