Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes
Laurent Roybon,
Nuno J. Lamas,
Alejandro Garcia-Diaz,
Eun Ju Yang,
Rita Sattler,
Vernice Jackson-Lewis,
Yoon A. Kim,
C. Alan Kachel,
Jeffrey D. Rothstein,
Serge Przedborski,
Hynek Wichterle,
Christopher E. Henderson
Affiliations
Laurent Roybon
Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University Medical Center, P&S 16-440, 630 West 168th Street, New York, NY 10032, USA
Nuno J. Lamas
Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University Medical Center, P&S 16-440, 630 West 168th Street, New York, NY 10032, USA
Alejandro Garcia-Diaz
Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University Medical Center, P&S 16-440, 630 West 168th Street, 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 Jackson-Lewis
Columbia Stem Cell Initiative (CSCI), Departments of Pathology and Cell Biology and Neurology, Center for Motor Neuron Biology and Disease (MNC), Columbia University Medical Center, P&S 5-420, 630 West 168th Street, New York, NY 10032, USA
Yoon A. Kim
Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University Medical Center, P&S 16-440, 630 West 168th Street, New York, NY 10032, USA
C. Alan Kachel
Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University Medical Center, P&S 16-440, 630 West 168th Street, 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
Columbia Stem Cell Initiative (CSCI), Departments of Pathology and Cell Biology and Neurology, Center for Motor Neuron Biology and Disease (MNC), Columbia University Medical Center, P&S 5-420, 630 West 168th Street, New York, NY 10032, USA
Hynek Wichterle
Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University Medical Center, P&S 16-440, 630 West 168th Street, New York, NY 10032, USA
Christopher E. Henderson
Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University Medical Center, P&S 16-440, 630 West 168th Street, New York, NY 10032, USA
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.
