Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain; Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands; Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
Prog Neurobiol. 2018 Sep;168:42-68. doi: 10.1016/j.pneurobio.2018.04.003. Epub 2018 Apr 10.
Human pluripotent stem cell (PSC) technology and direct somatic cell reprogramming have opened up a promising new avenue in the field of neuroscience. These recent advances allow researchers to obtain virtually any cell type found in the human brain, making it possible to produce and study functional neurons in laboratory conditions for both scientific and medical purposes. Although distinct approaches have shown to be successful in directing neuronal cell fate in vitro, their refinement and optimization, as well as the search for alternative approaches, remains necessary to help realize the full potential of the eventually derived neuronal populations. Furthermore, we are currently limited in the number of neuronal subtypes whose induction is fully established, and different cultivation protocols for each subtype exist, making it challenging to increase the reproducibility and decrease the variances that are observed between different protocols. In this review, we summarize the progress that has been made in generating various neuronal subtypes from PSCs and somatic cells, with special emphasis on chemically defined systems, transcription factor-mediated reprogramming and epigenetic-based approaches. We also discuss the efforts that are being made to increase the efficiency of current protocols and address the potential for the use of these cells in disease modelling, drug discovery and regenerative medicine.
人多能干细胞（PSC）技术和直接体细胞重编程在神经科学领域开辟了一条有前景的新途径。这些新的进展使得研究人员能够获得人类大脑中几乎任何类型的细胞，从而可以在实验室条件下产生和研究功能性神经元，用于科学和医学目的。尽管不同的方法已被证明可以成功地在体外指导神经元细胞命运，但仍需要对其进行细化和优化，并寻找替代方法，以帮助充分发挥最终衍生的神经元群体的潜力。此外，我们目前受到限制，能够完全确定诱导的神经元亚型的数量有限，并且每种亚型都存在不同的培养方案，这使得增加可重复性和减少不同方案之间观察到的差异变得具有挑战性。在这篇综述中，我们总结了从 PSC 和体细胞生成各种神经元亚型的进展，特别强调了化学定义系统、转录因子介导的重编程和基于表观遗传的方法。我们还讨论了提高现有方案效率的努力，并探讨了这些细胞在疾病建模、药物发现和再生医学中的应用潜力。
