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

doi:10.1016/j.stemcr.2017.06.018

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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289 Scopus citations

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 language	English
Pages (from-to)	600-614
Number of pages	15
Journal	Stem Cell Reports
Volume	9
Issue number	2
DOIs	https://doi.org/10.1016/j.stemcr.2017.06.018
State	Published - Aug 8 2017

Keywords

astrocyte
human induced pluripotent stem cell
iPSC

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10.1016/j.stemcr.2017.06.018

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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

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title = "An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells",

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.",

keywords = "astrocyte, human induced pluripotent stem cell, iPSC",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = aug,

day = "8",

doi = "10.1016/j.stemcr.2017.06.018",

language = "English",

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AU - TCW, Julia

AU - Wang, Minghui

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AU - Hartley, Brigham J.

AU - Lacin, Emre

AU - Machlovi, Saima I.

AU - Abdelaal, Rawan

AU - Karch, Celeste M.

AU - Phatnani, Hemali

AU - Slesinger, Paul A.

AU - Zhang, Bin

AU - Goate, Alison M.

AU - Brennand, Kristen J.

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AB - 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.

KW - astrocyte

KW - human induced pluripotent stem cell

KW - iPSC

UR - https://www.scopus.com/pages/publications/85026318812

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DO - 10.1016/j.stemcr.2017.06.018

M3 - Article

C2 - 28757165

AN - SCOPUS:85026318812

SN - 2213-6711

VL - 9

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EP - 614

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 2

ER -

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

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