Jiménez-Moreno Natalia, Stathakos Petros, Caldwell Maeve A, Lane Jon D
Cell Biology Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
Trinity College Institute for Neuroscience, Trinity College, Dublin 2, Ireland.
Cells. 2017 Aug 11;6(3):24. doi: 10.3390/cells6030024.
Human induced pluripotent stem cells (hiPSCs) are invaluable tools for research into the causes of diverse human diseases, and have enormous potential in the emerging field of regenerative medicine. Our ability to reprogramme patient cells to become hiPSCs, and to subsequently direct their differentiation towards those classes of neurons that are vulnerable to stress, is revealing how genetic mutations cause changes at the molecular level that drive the complex pathogeneses of human neurodegenerative diseases. Autophagy dysregulation is considered to be a major contributor in neural decline during the onset and progression of many human neurodegenerative diseases, meaning that a better understanding of the control of non-selective and selective autophagy pathways (including mitophagy) in disease-affected classes of neurons is needed. To achieve this, it is essential that the methodologies commonly used to study autophagy regulation under basal and stressed conditions in standard cell-line models are accurately applied when using hiPSC-derived neuronal cultures. Here, we discuss the roles and control of autophagy in human stem cells, and how autophagy contributes to neural differentiation in vitro. We also describe how autophagy-monitoring tools can be applied to hiPSC-derived neurons for the study of human neurodegenerative disease in vitro.
人类诱导多能干细胞（hiPSC）是研究多种人类疾病病因的宝贵工具，在新兴的再生医学领域具有巨大潜力。我们将患者细胞重编程为hiPSC，并随后将其诱导分化为易受应激影响的神经元类别的能力，正在揭示基因突变如何在分子水平上引发变化，从而驱动人类神经退行性疾病的复杂发病机制。自噬失调被认为是许多人类神经退行性疾病发生和进展过程中神经功能衰退的主要原因，这意味着需要更好地了解疾病影响的神经元类别中非选择性和选择性自噬途径（包括线粒体自噬）的调控机制。为了实现这一点，在使用hiPSC衍生的神经元培养物时，准确应用标准细胞系模型中常用于研究基础和应激条件下自噬调控的方法至关重要。在这里，我们讨论自噬在人类干细胞中的作用和调控，以及自噬如何在体外促进神经分化。我们还描述了自噬监测工具如何应用于hiPSC衍生的神经元，以在体外研究人类神经退行性疾病。
