GPI-80 defines self-renewal ability in hematopoietic stem cells during human development.
GPI-80 defines self-renewal ability in hematopoietic stem cells during human development.
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DOI：
10.1016/j.stem.2014.10.020
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发表时间：
2015-01-08
期刊：
影响因子：
23.9
通讯作者：
Mikkola HK
中科院分区：
文献类型：
--
作者：
Prashad SL;Calvanese V;Yao CY;Kaiser J;Wang Y;Sasidharan R;Crooks G;Magnusson M;Mikkola HK
多能干细胞和重编程技术的进步为培养造血干细胞（HSC）带来了希望。为了取得成功，需要更好地了解人类发育过程中自我更新的HSC。我们发现糖磷脂酰肌醇锚定的表面蛋白GPI-80定义了具有自我更新能力的人胎肝造血干/祖细胞（HSPC）亚群。CD 34 + CD 38 lo/− CD 90 +GPI-80+ HSPC是在基质共培养物中维持增殖潜力和未分化状态并移植到免疫缺陷小鼠中的唯一群体。GPI-80表达还使得一旦HSPC从内皮出现并在人胎儿造血小生境之间迁移，就能够追踪HSPC。GPI-80与整联蛋白α-M（ITGAM）共定位于HSPC的表面上，所述整联蛋白α-M在白细胞中与GPI-80协作以支持迁移。GPI-80或ITGAM的敲低足以损害培养物中的HSPC扩增和体内植入。这些发现表明人胎儿HSC采用白细胞粘附和迁移机制来介导HSC自我更新。
Advances in pluripotent stem cell and reprogramming technologies have given hope of generating hematopoietic stem cells (HSC) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that glycophosphatidylinositol-anchored surface protein GPI-80 defines a subpopulation of human fetal liver hematopoietic stem/progenitor cells (HSPC) with self-renewal ability. CD34+CD38lo/−CD90+GPI-80+ HSPC were the sole population that maintained proliferative potential and undifferentiated state in stroma co-culture and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSPC once they have emerged from endothelium and migrate between human fetal hematopoietic niches. GPI-80 co-localized on the surface of HSPC with Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration. Knockdown of GPI-80 or ITGAM was sufficient to compromise HSPC expansion in culture and engraftment in vivo. These findings indicate that human fetal HSC employ mechanisms used in leukocyte adhesion and migration to mediate HSC self-renewal.