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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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