Cao Huimin, Heazlewood Shen Y, Williams Brenda, Cardozo Daniela, Nigro Julie, Oteiza Ana, Nilsson Susan K
Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), Melbourne, Australia Australian Regenerative Medicine Institute, Monash University, Melbourne, Australia.
Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), Melbourne, Australia.
Haematologica. 2016 Jan;101(1):26-37. doi: 10.3324/haematol.2015.135921. Epub 2015 Nov 6.
Throughout development, hematopoietic stem cells migrate to specific microenvironments, where their fate is, in part, extrinsically controlled. CD44 standard as a member of the cell adhesion molecule family is extensively expressed within adult bone marrow and has been previously reported to play important roles in adult hematopoietic regulation via CD44 standard-ligand interactions. In this manuscript, CD44 expression and function are further assessed and characterized on both fetal and adult hematopoietic stem cells. Using a CD44(-/-) mouse model, conserved functional roles of CD44 are revealed throughout development. CD44 is critical in the maintenance of hematopoietic stem and progenitor pools, as well as in hematopoietic stem cell migration. CD44 expression on hematopoietic stem cells as well as other hematopoietic cells within the bone marrow microenvironment is important in the homing and lodgment of adult hematopoietic stem cells isolated from the bone/bone marrow interface. CD44 is also involved in fetal hematopoietic stem cell migration out of the liver, via a process involving stromal cell-derived factor-1α. The absence of CD44 in neonatal bone marrow has no impact on the size of the long-term reconstituting hematopoietic stem cell pool, but results in an enhanced long-term engraftment potential of hematopoietic stem cells.
在整个发育过程中，造血干细胞迁移至特定的微环境，其命运在一定程度上受到外在因素的控制。作为细胞黏附分子家族成员之一的CD44标准型在成年骨髓中广泛表达，此前有报道称其通过CD44标准型-配体相互作用在成年造血调节中发挥重要作用。在本论文中，对胎儿和成年造血干细胞的CD44表达及功能进行了进一步评估和表征。利用CD44基因敲除小鼠模型，揭示了CD44在整个发育过程中的保守功能作用。CD44对于维持造血干细胞和祖细胞库以及造血干细胞迁移至关重要。造血干细胞以及骨髓微环境中其他造血细胞上的CD44表达对于从骨/骨髓界面分离的成年造血干细胞的归巢和定居很重要。CD44还通过涉及基质细胞衍生因子-1α的过程参与胎儿造血干细胞从肝脏迁出。新生骨髓中缺乏CD44对长期重建造血干细胞库的大小没有影响，但会导致造血干细胞的长期植入潜力增强。
