Human Stem Cell-Derived Spinal Cord Astrocytes with Defined Mature or Reactive Phenotypes

• 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

SummaryDifferentiation 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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