Wilkens Ruven, Korffmann Jürgen, Nicolaisen Nathalie, Modic Tjasa Lepko, Roewe Julian, Habich Carina, Bahnassawy Lamiaa, Cik Miroslav, Reinhardt Peter
AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
Methods Mol Biol. 2025;2924:17-29. doi: 10.1007/978-1-0716-4530-7_2.
Neurodegenerative diseases such as Alzheimer's or Parkinson's are marked by progressive loss of affected neurons. Even with novel disease-modifying therapies, this loss cannot be reversed. In situ astrocyte-to-neuron (AtN) transdifferentiation may provide an opportunity to convert resident astrocytes into new neurons to revert the loss of neurons incurred. Currently, most studies investigating AtN transdifferentiation in vitro rely on the use of primary mouse astrocyte cultures which require sacrificing animals and come with uncertainty regarding species differences. Conversely, human induced pluripotent stem cell (hiPSC)-derived astrocytes offer the advantage of working in a human cell culture system which improves translatability and provides the opportunity to generate large, cryopreservable batches of cells to identify and study conversion factors. This protocol details a workflow for assessing the suitability of potential conversion factors for transdifferentiating hiPSC-derived astrocytes into neurons.
诸如阿尔茨海默病或帕金森病等神经退行性疾病的特征是受影响的神经元逐渐丧失。即使采用新型疾病修饰疗法，这种丧失也无法逆转。原位星形胶质细胞向神经元（AtN）转分化可能提供一个机会，将常驻星形胶质细胞转化为新的神经元，以恢复所发生的神经元丧失。目前，大多数体外研究AtN转分化的实验依赖于使用原代小鼠星形胶质细胞培养物，这需要牺牲动物，并且存在物种差异的不确定性。相反，人诱导多能干细胞（hiPSC）衍生的星形胶质细胞具有在人类细胞培养系统中工作的优势，这提高了可转化性，并提供了生成大量可冷冻保存的细胞批次以识别和研究转化因子的机会。本方案详细介绍了一种工作流程，用于评估将hiPSC衍生的星形胶质细胞转分化为神经元的潜在转化因子的适用性。
