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

Research output: Contribution to journal › Article › peer-review

291 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",

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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

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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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