Human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes

Laurent Roybon, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, New York, NY 10032, USA.
Nuno J. Lamas, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, New York, NY 10032, USA.
Alejandro D. Garcia, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, New York, NY 10032, USA.
Eun Ju Yang, Brain Science Institute and Department of Neurology, Johns Hopkins University, 855 N Wolfe Street, Rangos 2-223, Baltimore, MD 21205, USA.
Rita Sattler, Brain Science Institute and Department of Neurology, Johns Hopkins University, 855 N Wolfe Street, Rangos 2-223, Baltimore, MD 21205, USA.
Vernice J. Lewis, Departments of Pathology and Cell Biology, and Neurology, Center for Motor Neuron Biology and Disease (MNC), Columbia Stem Cell Initiative (CSCI) Columbia University Medical Center, New York, NY 10032, USA.
Yoon A. Kim, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, New York, NY 10032, USA.
C Alan Kachel, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, New York, NY 10032, USA.
Jeffrey D. Rothstein, Brain Science Institute and Department of Neurology, Johns Hopkins University, 855 N Wolfe Street, Rangos 2-223, Baltimore, MD 21205, USA.
Serge Przedborski, Departments of Pathology and Cell Biology, and Neurology, Center for Motor Neuron Biology and Disease (MNC), Columbia Stem Cell Initiative (CSCI) Columbia University Medical Center, New York, NY 10032, USA.
Hynek Wichterle, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, New York, NY 10032, USA.
Christopher E. Henderson, Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, New York, NY 10032, USA.

Document Type

Article

Abstract

Differentiation of astrocytes from human stem cells has significant potential for analysis of their role in normal brain function and disease, but existing protocols generate only immature astrocytes. Using early neuralization, we generated spinal cord astrocytes from mouse or human embryonic or induced pluripotent stem cells with high efficiency. Remarkably, short exposure to fibroblast growth factor 1 (FGF1) or FGF2 was sufficient to direct these astrocytes selectively toward a mature quiescent phenotype, as judged by both marker expression and functional analysis. In contrast, tumor necrosis factor alpha and interleukin-1β, but not FGFs, induced multiple elements of a reactive inflammatory phenotype but did not affect maturation. These phenotypically defined, scalable populations of spinal cord astrocytes will be important both for studying normal astrocyte function and for modeling human pathological processes in vitro.

Medical Subject Headings

Animals; Astrocytes (cytology, metabolism); Cell Differentiation (physiology); Cells, Cultured; Humans; Mice; Neural Stem Cells (cytology, metabolism); Neurons (cytology, metabolism, pathology); Phenotype; Pluripotent Stem Cells (cytology, metabolism); Spinal Cord (cytology, metabolism)

Publication Date

9-12-2013

Publication Title

Cell reports

E-ISSN

2211-1247

Volume

4

Issue

5

First Page

1035

Last Page

1048

PubMed ID

23994478

Digital Object Identifier (DOI)

10.1016/j.celrep.2013.06.021

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