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An Efficient Platform For Astrocyte Differentiation From Human Induced Pluripotent Stem Cells

By TCW Julia, Minghui Wang, Anna A Pimenova, Kathryn R. Bowles, Brigham J. Hartley, Emre Lacin, Saima Machlovi, Rawan Abdelaal, Celeste M. Karch, Hemali Phetnani, Paul A. Slesinger, Bin Zhang, Alison M. Goate, Kristen J. Brennand

Posted 03 May 2017
bioRxiv DOI: 10.1101/133496 (published 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. Using this method, we generated hiPSC-derived astrocyte populations (hiPSC-astrocytes) from 42 NPC lines (derived from 30 individuals) with an average of ~90% S100β-positive cells. Transcriptomic analysis demonstrated that the hiPSC-astrocytes 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 novel protocol is a reproducible, straightforward (single media) and rapid (<30 days) method to generate homogenous populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders.

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