Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells
Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells
复制标题
DOI：
10.1016/j.celrep.2016.04.061
复制
发表时间：
2016-05-24
期刊：
影响因子：
8.8
通讯作者：
Lu, Rong
中科院分区：
文献类型：
--
作者：
Brewer, Casey;Chu, Elizabeth;Lu, Rong
造血干细胞（HSC）移植是最普遍的干细胞治疗，但它仍然是一个危险的程序。为了改善这种治疗，重要的是要了解移植的干细胞如何重建血液和免疫系统，以及这一过程如何受到移植变量（如HSC剂量）的影响。在这里，我们发现，在移植后的长期内，70%-80%的供体HSC衍生的克隆不产生所有测量的血细胞类型。高HSC剂量导致更多的克隆表现出平衡的淋巴细胞产生，而低剂量产生更多的T细胞特异性克隆。与低剂量相比，高HSC剂量还产生显著更高比例的早期分化克隆。这些复杂的分化行为揭示了造血再生的克隆水平再生动力学，并表明移植剂量可用于改善干细胞治疗。
Hematopoietic stem cell (HSC) transplantation is the most prevalent stem cell therapy, but it remains a risky procedure. To improve this treatment, it is important to understand how transplanted stem cells rebuild the blood and immune systems and how this process is impacted by transplantation variables such as the HSC dose. Here, we find that, in the long term following transplantation, 70%-80% of donor-HSC-derived clones do not produce all measured blood cell types. High HSC doses lead to more clones that exhibit balanced lymphocyte production, whereas low doses produce more T-cell-specialized clones. High HSC doses also produce significantly higher proportions of early-differentiating clones compared to low doses. These complex differentiation behaviors uncover the clonal-level regeneration dynamics of hematopoietic regeneration and suggest that transplantation dose can be exploited to improve stem cell therapy.