Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse

祖细胞和成熟人类星形胶质细胞的纯化和表征揭示了与小鼠的转录和功能差异

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作者:Ye Zhang, Steven A Sloan, Laura E Clarke, Christine Caneda, Colton A Plaza, Paul D Blumenthal, Hannes Vogel, Gary K Steinberg, Michael S B Edwards, Gordon Li, John A Duncan 3rd, Samuel H Cheshier, Lawrence M Shuer, Edward F Chang, Gerald A Grant, Melanie G Hayden Gephart, Ben A Barres

Abstract

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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