Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes
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 in...
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doaj-be71f644a0784f3d84839de4950e41392020-11-24T23:54:38ZengElsevierCell Reports2211-12472013-09-01451035104810.1016/j.celrep.2013.06.021Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive PhenotypesLaurent Roybon0Nuno J. Lamas1Alejandro Garcia-Diaz2Eun Ju Yang3Rita Sattler4Vernice Jackson-Lewis5Yoon A. Kim6C. Alan Kachel7Jeffrey D. Rothstein8Serge Przedborski9Hynek Wichterle10Christopher E. Henderson11Project 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, USAProject 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, USAProject 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, USABrain Science Institute and Department of Neurology, Johns Hopkins University, 855 N Wolfe Street, Rangos 2-223, Baltimore, MD 21205, USABrain Science Institute and Department of Neurology, Johns Hopkins University, 855 N Wolfe Street, Rangos 2-223, Baltimore, MD 21205, USAColumbia 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, USAProject 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, USAProject 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, USABrain Science Institute and Department of Neurology, Johns Hopkins University, 855 N Wolfe Street, Rangos 2-223, Baltimore, MD 21205, USAColumbia 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, USAProject 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, USAProject 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. http://www.sciencedirect.com/science/article/pii/S2211124713003136 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes Cell Reports |
author_facet |
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 |
author_sort |
Laurent Roybon |
title |
Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes |
title_short |
Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes |
title_full |
Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes |
title_fullStr |
Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes |
title_full_unstemmed |
Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes |
title_sort |
human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-09-01 |
description |
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.
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url |
http://www.sciencedirect.com/science/article/pii/S2211124713003136 |
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