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

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

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Abstract

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.

Original languageEnglish
Pages (from-to)600-614
Number of pages15
JournalStem Cell Reports
Volume9
Issue number2
DOIs
StatePublished - Aug 8 2017

Keywords

  • astrocyte
  • human induced pluripotent stem cell
  • iPSC

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    TCW, J., Wang, M., Pimenova, A. A., Bowles, K. R., Hartley, B. J., Lacin, E., Machlovi, S. I., Abdelaal, R., Karch, C. M., Phatnani, H., Slesinger, P. A., Zhang, B., Goate, A. M., & Brennand, K. J. (2017). An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells. Stem Cell Reports, 9(2), 600-614. https://doi.org/10.1016/j.stemcr.2017.06.018