Cell Reports
Volume 4, Issue 5, 12 September 2013, Pages 1035-1048
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Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes

https://doi.org/10.1016/j.celrep.2013.06.021Get rights and content
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Highlights

  • Spinal cord astrocytes can be generated from human ESCs/iPSCs using early neuralization

  • ESC/hiPSC-derived astrocytes are immature, but FGF1 and FGF2 induce rapid maturation

  • TNFα and IL-1β selectively induce a reactive phenotype in hESC/iPSC-derived astrocytes

  • Human astrocytes provide a model for studying glial biology and modeling disease

Summary

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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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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These authors contributed equally to this work

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Present address: Stem Cell Laboratory for CNS Disease Modeling, Department of Experimental Medical Science, Lund University, Lund 22184, Sweden

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Present address: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho Braga, Portugal