PLX122214

GSE147191: Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome Model

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Despite advances in understanding the pathophysiology of Fragile X syndrome (FXS), its molecular bases are still poorly understood. We performed single cell RNA-seq from the cortex of both Fmr1-knock out (Fmr1-KO) and wild type (WT) FVB animals at postnatal day 5. After stringent filtering, we obtained 18,393 cells for which we detected an average of 1,778 genes and 3,988 transcripts. We identified a total of 18 distinct populations, these include vascular cells (endothelial cells and pericytes), fibroblasts, ependymal cells, different neuron subtypes and glial cells. Our findings present new insights into the cell type specific consequences of FXS. We found that FXS results in a highly cell type specific effect and it is strongest among different neuronal types. We detected a downregulation of mRNAs bound by FMRP and this effect is prominent in neurons. Metabolic pathways including translation are significantly upregulated across all cell types with the notable exception of excitatory neurons. These effects point to a potential difference in the activity of mTOR pathways, and together with other dysregulated pathways suggest an excitatory-inhibitory imbalance in the FXS cortex which is exacerbated by astrocytes. Our data demonstrate the cell-type specific complexity of FXS and provide a resource for interrogating the biological basis of this disorder. SOURCE: Elisa DonnardGarber University of Massachusetts Medical School