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An efficient platform for astrocyte differentiation from human induced pluripotent stem cells

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
doi: https://doi.org/10.1101/133496
TCW Julia
1Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
2Ronald M. Loeb Center for Alzheimer’s disease, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
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Minghui Wang
4Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029, USA
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Anna A. Pimenova
1Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
2Ronald M. Loeb Center for Alzheimer’s disease, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
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Kathryn R. Bowles
1Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
2Ronald M. Loeb Center for Alzheimer’s disease, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
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Brigham J. Hartley
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
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Emre Lacin
1Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
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Saima Machlovi
1Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
2Ronald M. Loeb Center for Alzheimer’s disease, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
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Rawan Abdelaal
5New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA
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Celeste M. Karch
6Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA
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Hemali Phetnani
5New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA
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Paul A. Slesinger
1Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
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Bin Zhang
4Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029, USA
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Alison M. Goate
1Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
2Ronald M. Loeb Center for Alzheimer’s disease, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
4Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, New York, NY 10029, USA
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  • For correspondence: alison.goate@mssm.edu kristen.brennand@mssm.edu
Kristen J. Brennand
1Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY 10029, USA
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  • For correspondence: alison.goate@mssm.edu kristen.brennand@mssm.edu
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SUMMARY

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.

hiPSC
human induced pluripotent stem cell
NPC
neural progenitor cell
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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 03, 2017.
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An efficient platform for astrocyte differentiation from human induced pluripotent stem cells
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
bioRxiv 133496; doi: https://doi.org/10.1101/133496
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An efficient platform for astrocyte differentiation from human induced pluripotent stem cells
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
bioRxiv 133496; doi: https://doi.org/10.1101/133496

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