title: Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.
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.
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: zhangye@stanford.edu.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Sloan
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Clarke
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Caneda
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Colton A
authors.initials: CA
authors.lastname: Plaza
authors.affiliation: Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Blumenthal
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Department of Neurosurgery, Lucile Packard Children's Hospital and Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Steinberg
authors.affiliation: Department of Neurosurgery, Lucile Packard Children's Hospital and Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Michael S B
authors.initials: MS
authors.lastname: Edwards
authors.affiliation: Department of Neurosurgery, Lucile Packard Children's Hospital and Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Gordon
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pediatric Neurosciences, Kaiser Permanente Santa Clara Medical Center, Santa Clara, CA 95051, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Duncan
authors.affiliation: Department of Neurosurgery, Lucile Packard Children's Hospital and Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Cheshier
authors.affiliation: Department of Neurosurgery, Lucile Packard Children's Hospital and Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Shuer
authors.affiliation: UCSF Epilepsy Center, University of California, San Francisco, 400 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Lucile Packard Children's Hospital and Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Grant
authors.affiliation: Department of Neurosurgery, Lucile Packard Children's Hospital and Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Melanie G Hayden
authors.initials: MG
authors.lastname: Gephart
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Barres
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001921:Brain / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D017628:Microglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology; D059467:Transcriptome / Q000502:physiology