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Neuron. 2016 Jan 6;89(1):37-53. doi: 10.1016/j.neuron.2015.11.013. Epub 2015 Dec 10.

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

Author information

1
Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: zhangye@stanford.edu.
2
Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA 94305, USA.
4
Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.
5
Department of Neurosurgery, Lucile Packard Children's Hospital and Stanford University Medical Center, Stanford, CA 94305, USA.
6
Department of Pediatric Neurosciences, Kaiser Permanente Santa Clara Medical Center, Santa Clara, CA 95051, USA.
7
UCSF Epilepsy Center, University of California, San Francisco, 400 Parnassus Avenue, San Francisco, CA 94143, USA.

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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PMID:
26687838
PMCID:
PMC4707064
DOI:
10.1016/j.neuron.2015.11.013
[Indexed for MEDLINE]
Free PMC Article

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