Transcriptome analysis of oxdative-stress induced senescence in human astrocytes

Purpose: Cellular senescence is a cell stress response resulting in permanent growth arrest and the production of an altered pro-inflammatory secretory profile known as the senescecnce-associated secretory phenotype (SASP). The induction of senescence in astrocytes, a cell type responsible for maintaining homeostasis within the central nervous system (CNS) and responding to CNS insults, has been implicated in neurodegenerative disease. However, little is known about the senescent transcriptome in CNS-derived cell types including astrocytes. Methods: To better understand senescence-associated gene expression changes in astrocytes, we investigated global changes in the astrocyte transcriptome using RNA-seq following the induction of oxidative stress-induced senescence with hydrogen peroxide. Results: During senescence, we find evidence of a loss of brain expressed transcripts involved in diverse CNS processes including neuronal differentiation and development, gliogenesis, axonogenesis, and learning and memory as well as a loss of transcripts involved in MHC class II antigen processing and presentation. In addition, we find evidence for induction of the senescent phenotype including a loss of transcripts involved in cell division and an increase in the mRNA level of inflammatory mediators suggestive of a SASP. Conclusions: Overall, our findings suggest a loss of differentiated function in senescent astrocytes and a gain in neuroinflammatory function as part of the SASP as a potential mechanisms for dysfunction in the aging brain. Overall design: Examination of transcriptome changes by RNAseq in pre-senescent and senescent astrocytes using 2 biological replicates per condition

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Crowe EP, Tuzer F, Gregory BD, Donahue G, Gosai SJ, Cohen J, Leung YY, Yetkin E, Nativio R, Wang LS, Sell C, Bonini NM, Berger SL, Johnson FB, Torres C