title: Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence.
abstract: Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including glial fibrillary acidic protein and genes involved in the processing and presentation of antigens by major histocompatibility complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders.
authors.affiliation: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia PA, USA.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Crowe
authors.affiliation: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia PA, USA.
authors.forename: Ferit
authors.initials: F
authors.lastname: Tuzer
authors.affiliation: Department of Biology, Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Gregory
authors.affiliation: Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Donahue
authors.affiliation: Department of Biology, Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Sager J
authors.initials: SJ
authors.lastname: Gosai
authors.affiliation: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia PA, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Yuk Y
authors.initials: YY
authors.lastname: Leung
authors.affiliation: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia PA, USA.
authors.forename: Emre
authors.initials: E
authors.lastname: Yetkin
authors.affiliation: Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Nativio
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Li-San
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia PA, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Sell
authors.affiliation: Department of Biology, Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Bonini
authors.affiliation: Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
authors.forename: F Brad
authors.initials: FB
authors.lastname: Johnson
authors.affiliation: Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia PA, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Torres
keywords: RNA sequencing; astrocyte function; astrocyte senescence; brain aging; brain oxidative stress