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Heterogeneity of Notch signaling in astrocytes and the effects of GFAP and vimentin deficiency

Artikel i vetenskaplig tidskrift
Författare Isabell Lebkuechner
Ulrika Wilhelmsson
Elin Möllerström
Marcela Pekna
Milos Pekny
Publicerad i Journal of Neurochemistry
Volym 135
Nummer/häfte 2
Sidor 234-248
ISSN 0022-3042
Publiceringsår 2015
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Sidor 234-248
Språk en
Länkar dx.doi.org/10.1111/jnc.13213
Ämnesord astrocytes, GFAP, Notch signaling, single-cell gene expression profiling, vimentin, fibrillary acidic protein, neural stem-cells, central-nervous-system, intermediate-filament protein, factor hb-egf, reactive astrocytes, mice, deficient, growth-factor, progenitor cells, dentate gyrus, Biochemistry & Molecular Biology, Neurosciences & Neurology
Ämneskategorier Neurovetenskaper

Sammanfattning

Astrocytes have multiple roles in the CNS including control of adult neurogenesis. We recently showed that astrocyte inhibition of neurogenesis through Notch signaling depends on the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. Here, we used real-time quantitative PCR to analyze gene expression in individual mouse astrocytes in primary cultures and in GFAP(POS) or Aldh1L1(POS) astrocytes freshly isolated from uninjured, contralesional and lesioned hippocampus 4days after entorhinal cortex lesion. To determine the Notch signaling competence of individual astrocytes, we measured the mRNA levels of Notch ligands and Notch1 receptor. We found that whereas most cultured and freshly isolated astrocytes were competent to receive Notch signals, only a minority of astrocytes were competent to send Notch signals. Injury increased the fraction of astrocyte subpopulation unable to send and receive Notch signals, thus resembling primary astrocytes invitro. Astrocytes deficient of GFAP and vimentin showed decreased Notch signal sending competence and altered expression of Notch signaling pathway-related genes Dlk2, Notch1, and Sox2. Furthermore, we identified astrocyte subpopulations based on their mRNA and protein expression of nestin and HB-EGF. This study improves our understanding of astrocyte heterogeneity, and points to astrocyte cytoplasmic intermediate filaments as targets for neural cell replacement strategies.

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