Neuron
Volume 89, Issue 1, 6 January 2016, Pages 37-53
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Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse

https://doi.org/10.1016/j.neuron.2015.11.013Get rights and content
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Highlights

  • We develop the first method to acutely purify fetal and adult human astrocytes

  • We obtain transcriptome profiles of human neurons, glia, and vascular cells

  • While similar, human and mouse astrocytes have unique genomic and functional traits

  • Human astrocytes exist in at least two distinct developmental stages

Summary

The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here, we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. We found that human astrocytes have abilities similar to those of murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. Next, we performed RNA sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells (available at http://www.brainrnaseq.org). With these profiles, we identified novel human-specific astrocyte genes and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell-type-specific molecular profiles of the healthy and diseased human brain.

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