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  • A cell type‐specific expres...
    Iemolo, Attilio; Montilla‐Perez, Patricia; Lai, I‐Chi; Meng, Yinuo; Nolan, Syreeta; Wen, Junneng; Rusu, Iulia; Dulcis, Davide; Telese, Francesca

    Journal of comparative neurology (1911), September 1, 2020, Letnik: 528, Številka: 13
    Journal Article

    The ability to rapidly change gene expression patterns is essential for differentiation, development, and functioning of the brain. Throughout development, or in response to environmental stimuli, gene expression patterns are tightly regulated by the dynamic interplay between transcription activators and repressors. Nuclear receptor corepressor 1 (NCoR1) and silencing mediator for retinoid or thyroid‐hormone receptors (SMRT) are the best characterized transcriptional co‐repressors from a molecular point of view. They mediate epigenetic silencing of gene expression in a wide range of developmental and homeostatic processes in many tissues, including the brain. For instance, NCoR1 and SMRT regulate neuronal stem cell proliferation and differentiation during brain development and they have been implicated in learning and memory. However, we still have a limited understanding of their regional and cell type‐specific expression in the brain. In this study, we used fluorescent immunohistochemistry to map their expression patterns throughout the adult mouse brain. Our findings reveal that NCoR1 and SMRT share an overall neuroanatomical distribution, and are detected in both excitatory and inhibitory neurons. However, we observed striking differences in their cell type‐specific expression in glial cells. Specifically, all oligodendrocytes express NCoR1, but only a subset express SMRT. In addition, NCoR1, but not SMRT, was detected in a subset of astrocytes and in the microglia. These novel observations are corroborated by single cell transcriptomics and emphasize how NCoR1 and SMRT may contribute to distinct biological functions, suggesting an exclusive role of NCoR1 in innate immune responses in the brain. Schematic representation of NCoR1 and SMRT distribution in neuronal and non‐neuronal cell types. Five major types of brain cells (glutamatergic and GABAergic neurons, astrocytes, oligodendrocytes, and microglia) are depicted within a representative coronal slice of the mouse brain. Both NCor1 and SMRT broadly localize within the nuclei of most neuronal cells. However, a diverse pattern of expression is detected in non‐neuronal cells. While NCoR1 is expressed in a small fraction of astrocytes, SMRT is not expressed in GFAP+ astrocytes or in Iba1+ microglia.