Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse

Article, Other literature type English OPEN
Zhang, Ye ; Sloan, Steven A. ; Clarke, Laura E. ; Caneda, Christine ; Plaza, Colton A. ; Blumenthal, Paul D. ; Vogel, Hannes ; Steinberg, Gary K. ; Edwards, Michael S. B. ; Li, Gordon ; Duncan, John A. ; Cheshier, Samuel H. ; Shuer, Lawrence M. ; Chang, Edward F. ; Grant, Gerald A. ; Hayden Gephart, Melanie G. ; Barres, Ben A. (2015)
  • Publisher: Elsevier BV
  • Journal: Neuron, volume 89, issue 1, pages 37-53 (issn: 0896-6273)
  • Related identifiers: doi: 10.1016/j.neuron.2015.11.013
  • Subject: Neuroscience(all) | Article

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 similar abilities to 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. We next 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. 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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