An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells

• Published in: Stem cell reports Vol. 9; no. 2; pp. 600 - 614
• Main Authors: TCW, Julia, Wang, Minghui, Pimenova, Anna A., Bowles, Kathryn R., Hartley, Brigham J., Lacin, Emre, Machlovi, Saima I., Abdelaal, Rawan, Karch, Celeste M., Phatnani, Hemali, Slesinger, Paul A., Zhang, Bin, Goate, Alison M., Brennand, Kristen J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.08.2017; Elsevier
• Subjects: astrocyte; Astrocytes - cytology; Astrocytes - metabolism; Calcium - metabolism; Cell Culture Techniques; Cell Differentiation - genetics; Cells, Cultured; Computational Biology - methods; Cytokines - metabolism; Gene Expression Profiling; Gene Expression Regulation, Developmental; human induced pluripotent stem cell; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; iPSC; Microglia - immunology; Microglia - metabolism; Molecular Sequence Annotation; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Phagocytosis; Transcriptome; human induced pluripotent stem cell; astrocyte; iPSC
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2017.06.018

Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. •hiPSC-derived astrocyte populations generated from 42 NPC lines•Transcriptomic analysis shows hiPSC-astrocytes resemble primary human astrocytes•hiPSC-astrocyte transcription is consistent with a non-reactive state•hiPSC-astrocytes undergo inflammatory response and enhance microglial phagocytosis Brennand, Goate, and colleagues report a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs) via a neural progenitor cell (NPC) intermediate. hiPSC-astrocytes resemble primary human fetal astrocytes, have a transcriptional signature consistent with a non-reactive state, respond to inflammatory stimulants, and enhance microglial phagocytosis.