Kim Kathryn M, Thaqi Mentor, Peterson Daniel A, Marr Robert A
Center for Neurodegenerative Disease and Therapeutics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States.
Scholl College of Podiatric Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States.
Front Bioeng Biotechnol. 2021 Mar 12;9:658498. doi: 10.3389/fbioe.2021.658498. eCollection 2021.
Direct cellular reprogramming exhibits distinct advantages over reprogramming from an induced pluripotent stem cell intermediate. These include a reduced risk of tumorigenesis and the likely preservation of epigenetic data. direct reprogramming approaches primarily aim to model the pathophysiological development of neurological disease and identify therapeutic targets, while direct reprogramming aims to develop treatments for various neurological disorders, including cerebral injury and cancer. In both approaches, there is progress toward developing increased control of subtype-specific production of induced neurons. A majority of research primarily utilizes fibroblasts as the donor cells. However, there are a variety of other somatic cell types that have demonstrated the potential for reprogramming into induced neurons. This review highlights studies that utilize non-fibroblastic cell sources for reprogramming, such as astrocytes, olfactory ensheathing cells, peripheral blood cells, Müller glia, and more. We will examine benefits and obstructions for translation into therapeutics or disease modeling, as well as efficiency of the conversion. A summary of donor cells, induced neuron types, and methods of induction is also provided.
直接细胞重编程相对于从诱导多能干细胞中间体进行重编程具有明显优势。这些优势包括降低肿瘤发生风险以及可能保留表观遗传数据。直接重编程方法主要旨在模拟神经疾病的病理生理发展并确定治疗靶点,而直接重编程旨在开发针对各种神经疾病的治疗方法,包括脑损伤和癌症。在这两种方法中,在加强对诱导神经元亚型特异性产生的控制方面都取得了进展。大多数研究主要利用成纤维细胞作为供体细胞。然而,还有多种其他体细胞类型已证明具有重编程为诱导神经元的潜力。本综述重点介绍了利用非成纤维细胞来源进行重编程的研究,如星形胶质细胞、嗅鞘细胞、外周血细胞、穆勒胶质细胞等。我们将研究转化为治疗方法或疾病模型的益处和障碍,以及转化效率。还提供了供体细胞、诱导神经元类型和诱导方法的总结。