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Sökning: L773:2213 6711 > (2018)

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  • Danesi, Claudia, et al. (författare)
  • Increased Calcium Influx through L-type Calcium Channels in Human and Mouse Neural Progenitors Lacking Fragile X Mental Retardation Protein
  • 2018
  • Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 11:6, s. 1449-1461
  • Tidskriftsartikel (refereegranskat)abstract
    • The absence of FMR1 protein (FMRP) causes fragile X syndrome (FXS) and disturbed FMRP function is implicated in several forms of human psychopathology. We show that intracellular calcium responses to depolarization are augmented in neural progenitors derived from human induced pluripotent stem cells and mouse brain with FXS. Increased calcium influx via nifedipine-sensitive voltage-gated calcium (Ca-v) channels contributes to the exaggerated responses to depolarization and type 1 metabotropic glutamate receptor activation. The ratio of L-type/T-type Ca-v channel expression is increased in FXS progenitors and correlates with enhanced progenitor differentiation to glutamate-responsive cells. Genetic reduction of brain-derived neurotrophic factor in FXS mouse progenitors diminishes the expression of Ca-v channels and activity-dependent responses, which are associated with increased phosphorylation of the phospholipase C-gamma 1 site within TrkB receptors and changes of differentiating progenitor subpopulations. Our results show developmental effects of increased calcium influx via L-type Ca-v channels in FXS neural progenitors.
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  • Lundin, Anders, et al. (författare)
  • Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models
  • 2018
  • Ingår i: Stem Cell Reports. - : Cell Press. - 2213-6711. ; 10:3, s. 1030-1045
  • Tidskriftsartikel (refereegranskat)abstract
    • In vivo studies of human brain cellular function face challenging ethical and practical difficulties. Animal models are typically used but display distinct cellular differences. One specific example is astrocytes, recently recognized for contribution to neurological diseases and a link to the genetic risk factor apolipoprotein E (APOE). Current astrocytic in vitro models are questioned for lack of biological characterization. Here, we report human induced pluripotent stem cell (hiPSC)-derived astroglia (NES-Astro) developed under defined conditions through long-term neuroepithelial-like stem (ltNES) cells. We characterized NES-Astro and astrocytic models from primary sources, astrocytoma (CCF-STTG1), and hiPSCs through transcriptomics, proteomics, glutamate uptake, inflammatory competence, calcium signaling response, and APOE secretion. Finally, we assess modulation of astrocyte biology using APOE-annotated compounds, confirming hits of the cholesterol biosynthesis pathway in adult and hiPSC-derived astrocytes. Our data show large diversity among astrocytic models and emphasize a cellular context when studying astrocyte biology.
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  • Parmar, Malin (författare)
  • Women in Stem Cell Science: Part I
  • 2018
  • Ingår i: Stem Cell Reports. - 2213-6711. ; 11:3, s. 611-611
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Female scientists play important leadership roles in the field and with the International Society for Stem Cell Research. We asked a number of these top researchers to share their personal stories and reflect on their career paths. Part II of this series will run in the October 2018 issue of Stem Cell Reports.
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