Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA; Center for Genomic and Computational Biology, Duke University, Durham, NC 27708, USA.
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA; Center for Genomic and Computational Biology, Duke University, Durham, NC 27708, USA; Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Curr Opin Genet Dev. 2018 Oct;52:13-21. doi: 10.1016/j.gde.2018.05.001. Epub 2018 May 24.
The ability to reprogram cell lineage specification through the activity of master regulatory transcription factors has transformed disease modeling, drug screening, and cell therapy for regenerative medicine. Recent advances in the engineering of synthetic transcription factors to modulate endogenous gene expression networks and chromatin states have generated a new set of tools with unique advantages to study and enhance cell reprogramming methods. Several studies have applied synthetic transcription factors in various cell reprogramming paradigms in human and murine cells. Moreover, the adaption of CRISPR-based transcription factors for high-throughput screening will enable the systematic identification of optimal factors and gene network perturbations to improve current reprogramming protocols and enable conversion to more diverse, highly specified, and mature cell types. The rapid development of next-generation technologies with more robust and versatile functionality will continue to expand the application of synthetic transcription factors for cell reprogramming.
通过主调控转录因子的活性来重新编程细胞谱系特化的能力已经改变了疾病建模、药物筛选和再生医学的细胞治疗。最近在合成转录因子的工程设计方面取得了进展,可以调节内源性基因表达网络和染色质状态,为研究和增强细胞重编程方法提供了一套新的具有独特优势的工具。几项研究已经在人类和鼠类细胞的各种细胞重编程范例中应用了合成转录因子。此外,基于 CRISPR 的转录因子的适应高通量筛选将能够系统地识别最佳因子和基因网络扰动,以改进当前的重编程方案,并能够向更多样化、高度特化和成熟的细胞类型转化。具有更强大和多功能的下一代技术的快速发展将继续扩大合成转录因子在细胞重编程中的应用。