期刊
JOURNAL OF NEUROCHEMISTRY
卷 135, 期 2, 页码 234-248出版社
WILEY-BLACKWELL
DOI: 10.1111/jnc.13213
关键词
astrocytes; GFAP; Notch signaling; single-cell gene expression profiling; vimentin
资金
- Swedish Medical Research Council [11548]
- ALF Gothenburg [11392]
- AFA Research Foundation
- Soderberg's Foundations
- Sten A. Olsson Foundation for Research and Culture
- Hjarnfonden
- Hagstromer's Foundation Millennium
- Amlov's Foundation
- E. Jacobson's Donation Fund
- VINNOVA Health Program
- Swedish Stroke Foundation
- Swedish Society of Medicine
- Wilhelm and Martina Lundgren's Research Foundation
- Free Mason Foundation
- NanoNet COST Action [BM1002]
- EU FP 7 Program EduGlia [237956]
- EU FP 7 Program TargetBraIn [279017]
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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