Molecular Genetics of Stem Cells Laboratory.
Cell Signalling and Proteomics Research Unit, Institute of Research in Immunology and Cancer, and.
Blood. 2017 Jun 22;129(25):3344-3351. doi: 10.1182/blood-2016-11-750729. Epub 2017 Apr 13.
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.
一小部分人类脐血 CD34 细胞在暴露于造血干细胞(HSC)自我更新激动剂 UM171 时表达内皮蛋白 C 受体(EPCR/CD201/PROCR)。在本文中,我们表明,与 EPCR 阴性细胞相比,EPCR 阳性 UM171 处理的细胞在免疫抑制小鼠中表现出强大的多谱系重殖和连续重建能力。与其他干细胞标志物(如 CD38)不同,当细胞在培养中引入时,无论是否进行 UM171 处理,EPCR 的表达均得以维持。尽管工程过表达 EPCR 未能复制 UM171 对 HSC 活性的影响,但它的表达对于人 HSC 的重殖活性是必需的。总之,我们的结果表明,EPCR 是 UM171 扩增的人类脐血 HSC 的可靠且与细胞培养兼容的标志物。