Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
Early Drug Discovery Unit, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
Cells. 2022 Jan 24;11(3):399. doi: 10.3390/cells11030399.
Astrocytes play important roles in the function and survival of neuronal cells. Dysfunctions of astrocytes are associated with numerous disorders and diseases of the nervous system, including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Human-induced pluripotent stem cell (iPSC)-based approaches are becoming increasingly important for the study of the mechanisms underlying the involvement of astrocytes in non-cell autonomous processes of motor neuron degeneration in ALS. These studies must account for the molecular and functional diversity among astrocytes in different regions of the brain and spinal cord. It is essential that the most pathologically relevant astrocyte preparations are used when investigating non-cell autonomous mechanisms of either upper or lower motor neuron degeneration in ALS. Here, we describe the efficient and streamlined generation of human iPSC-derived astrocytes with molecular and biological properties similar to physiological astrocytes in the ventral spinal cord. These induced astrocytes exhibit spontaneous and ATP-induced calcium transients, and lack signs of overt activation. Human iPSC-derived astrocytes with ventral spinal cord features offer advantages over more generic astrocyte preparations for the study of both ventral spinal cord astrocyte biology and the involvement of astrocytes in mechanisms of lower motor neuron degeneration in ALS.
星形胶质细胞在神经元细胞的功能和存活中发挥着重要作用。星形胶质细胞功能障碍与神经系统的许多疾病和紊乱有关，包括运动神经元疾病，如肌萎缩侧索硬化症（ALS）。基于人诱导多能干细胞（iPSC）的方法对于研究星形胶质细胞在 ALS 中运动神经元退行性变的非细胞自主过程中的作用机制变得越来越重要。这些研究必须考虑到大脑和脊髓不同区域的星形胶质细胞在分子和功能上的多样性。在研究 ALS 中上下运动神经元退行性变的非细胞自主机制时，使用最具病理相关性的星形胶质细胞制剂是至关重要的。在这里，我们描述了高效且简化的方法，用于生成具有与腹侧脊髓中生理星形胶质细胞相似的分子和生物学特性的人 iPSC 衍生星形胶质细胞。这些诱导的星形胶质细胞表现出自发和 ATP 诱导的钙瞬变，并且没有明显激活的迹象。具有腹侧脊髓特征的人 iPSC 衍生星形胶质细胞在研究腹侧脊髓星形胶质细胞生物学以及星形胶质细胞在 ALS 中运动神经元退行性变机制中的作用方面优于更通用的星形胶质细胞制剂。
