McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Curr Opin Genet Dev. 2013 Oct;23(5):585-90. doi: 10.1016/j.gde.2013.04.007. Epub 2013 May 30.
Direct conversion of cellular fate provides a potential approach to generate cells of the hematopoietic lineage without the requisite reversion to a pluripotent state via somatic cell reprogramming. The utilization of this technology has enabled transcription factor-mediated conversion of somatic cell types to primitive and mature hematopoietic cells. Recent studies demonstrate that the direct conversion of somatic cells to the hematopoietic lineage likely requires the use of pioneer transcription factors to establish an accessible chromatin state that is responsive to enforced expression of hematopoietic-specific transcription factors, in combination with appropriate culture conditions that facilitate reprogramming. Developing adaptable, experimental strategies that incorporate these parameters should enable the efficient generation of human hematopoietic cells with translational potential.
直接细胞命运转换为在无需体细胞重编程回复到多能状态的情况下生成造血谱系细胞提供了一种潜在方法。该技术的利用已经使得转录因子介导的体细胞类型向原始和成熟造血细胞的转化成为可能。最近的研究表明，体细胞向造血谱系的直接转化可能需要使用先驱转录因子来建立可及的染色质状态，该状态对强制表达造血特异性转录因子有反应，同时结合适当的培养条件来促进重编程。开发适应性强的实验策略，纳入这些参数，应该能够有效地生成具有转化潜力的人类造血细胞。
