Engineering Hematopoietic Stem Cells: Lessons from Development.
Engineering Hematopoietic Stem Cells: Lessons from Development.
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DOI：
10.1016/j.stem.2016.05.016
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发表时间：
2016-06-02
期刊：
影响因子：
23.9
通讯作者：
Daley GQ
中科院分区：
文献类型：
--
作者：
Rowe RG;Mandelbaum J;Zon LI;Daley GQ
细胞工程使我们非常接近于获得患者特异性造血干细胞（HSC）的目标。虽然定向分化和转录因子介导的转化策略已经产生了具有多谱系潜力的祖细胞，但迄今为止，由于长期自我更新不足和分化后代功能不足，治疗级工程化HSC仍然难以实现。涉及斑马鱼和哺乳动物系统的跨物种方法提供了补充方法，以提高对天然HSC的理解。在这里，我们讨论了保守的发育时序过程在脊椎动物造血中的作用，强调了如何识别和操纵阶段特异性因素，指定HSC发育状态必须利用工程HSC治疗。
Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy.