Dysregulated cholesterol metabolism, aberrant excitability and altered cell cycle of astrocytes in fragile X syndrome
| Autor: | Baiyan Ren, Maria Burkovetskaya, Yoosun Jung, Lara Bergdolt, Steven Totusek, Veronica Martinez‐Cerdeno, Kelly Stauch, Zeljka Korade, Anna Dunaevsky |
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| Rok vydání: | 2023 |
| Předmět: |
Proteomics
Intellectual and Developmental Disabilities (IDD) Regenerative Medicine Article Fragile X Mental Retardation Protein Cellular and Molecular Neuroscience Rare Diseases Animals Humans 2.1 Biological and endogenous factors Stem Cell Research - Embryonic - Human Aetiology Pediatric Neurology & Neurosurgery Stem Cell Research - Induced Pluripotent Stem Cell Stem Cell Research - Induced Pluripotent Stem Cell - Human Cell Cycle Neurosciences Stem Cell Research Brain Disorders Cholesterol Neurology Astrocytes Fragile X Syndrome Neurological Biotechnology |
| Zdroj: | Glia Glia, vol 71, iss 5 |
| ISSN: | 1098-1136 0894-1491 |
| Popis: | Fragile X syndrome (FXS), the most prevalent heritable form of intellectual disability, is caused by the transcriptional silencing of the FMR1 gene. While neuronal contribution to FXS has been extensively studied in both animal and human-based models of FXS, the roles of astrocytes, a type of glial cells in the brain, are largely unknown. Here, we generated a human-based FXS model via differentiation of astrocytes from human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) and characterized their development, function, and proteomic profiles. We identified shortened cell cycle, enhanced Ca(2+) signaling, impaired sterol biosynthesis and pervasive alterations in the proteome of FXS astrocytes. Our work identified astrocytic impairments that could contribute to the pathogenesis of FXS and highlight astrocytes as a novel therapeutic target for FXS treatment. |
| Databáze: | OpenAIRE |
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