Department of Internal Medicine, and Strategic Center of Cell and Bio Therapy for Heart, Diabetes and Cancer, Seoul National University Hospital.
Circ J. 2022 Nov 25;86(12):1925-1933. doi: 10.1253/circj.CJ-21-0703. Epub 2021 Nov 3.
Advances in nuclear reprogramming technology have enabled the dedifferentiation and transdifferentiation of mammalian cells. Forced induction of the key transcription factors constituting a transcriptional network can convert cells back to their pluripotent status or directly to another cell fate without inducing pluripotency. To date, direct conversion to several cell types, including cardiomyocytes, various types of neurons, and pancreatic β-cells, has been reported. We previously demonstrated direct lineage reprogramming of adult fibroblasts into induced endothelial cells (iECs) in mice and humans. In contrast to induced pluripotent stem cells, for which there is consensus on the criteria defining pluripotency, such criteria have not yet been established in the field of direct conversion. We thus suggest that careful assessment of the status of converted cells using genetic and epigenetic profiling, various functional assays, and the use of multiple readouts is essential to determine successful conversion. As direct conversion does not go through pluripotent status, this technique can be utilized for therapeutic purposes without the risk of tumorigenesis. Further, direct conversion can be induced in vivo by gene delivery to the target tissue or organ in situ. Thus, direct conversion technology can be developed into cell therapy or gene therapy for regenerative purposes. Here, we review the potential and future directions of direct cell fate conversion and iECs.
核重编程技术的进步使哺乳动物细胞的去分化和转分化成为可能。强制诱导构成转录网络的关键转录因子可以使细胞回到多能状态，或者直接转分化为另一种细胞命运，而无需诱导多能性。迄今为止，已经有报道称可以直接将几种细胞类型转化为心肌细胞、各种类型的神经元和胰岛 β 细胞。我们之前在小鼠和人类中证明了成纤维细胞直接谱系重编程为诱导型内皮细胞（iEC）。与诱导多能干细胞不同，对于诱导多能干细胞，人们已经就定义多能性的标准达成共识，但在直接转化领域尚未建立这样的标准。因此，我们建议使用遗传和表观遗传分析、各种功能测定以及使用多种读数来仔细评估转化细胞的状态，这对于确定成功转化至关重要。由于直接转化不经过多能状态，因此这项技术可用于治疗目的，而不会有致癌的风险。此外，还可以通过基因传递将直接转化在体内诱导到靶组织或器官原位。因此，直接转化技术可用于再生目的的细胞治疗或基因治疗。在这里，我们综述了直接细胞命运转换和 iEC 的潜力和未来方向。
