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Publication : CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes.

First Author  Barbar L Year  2020
Journal  Neuron Volume  107
Issue  3 Pages  436-453.e12
PubMed ID  32485136 Mgi Jnum  J:339535
Mgi Id  MGI:6449465 Doi  10.1016/j.neuron.2020.05.014
Citation  Barbar L, et al. (2020) CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes. Neuron 107(3):436-453.e12
abstractText  New methods for investigating human astrocytes are urgently needed, given their critical role in the central nervous system. Here we show that CD49f is a novel marker for human astrocytes, expressed in fetal and adult brains from healthy and diseased individuals. CD49f can be used to purify fetal astrocytes and human induced pluripotent stem cell (hiPSC)-derived astrocytes. We provide single-cell and bulk transcriptome analyses of CD49f(+) hiPSC-astrocytes and demonstrate that they perform key astrocytic functions in vitro, including trophic support of neurons, glutamate uptake, and phagocytosis. Notably, CD49f(+) hiPSC-astrocytes respond to inflammatory stimuli, acquiring an A1-like reactive state, in which they display impaired phagocytosis and glutamate uptake and fail to support neuronal maturation. Most importantly, we show that conditioned medium from human reactive A1-like astrocytes is toxic to human and rodent neurons. CD49f(+) hiPSC-astrocytes are thus a valuable resource for investigating human astrocyte function and dysfunction in health and disease.
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