Combination of Omics Approaches to Study Molecular Abnormalities in Individual Brain Cell Types of a DM1 Mouse Model
Résumé
Introduction: Molecular mechanisms of DM1 muscle/cardiac pathology are better characterized than those implicated in CNS dysfunction. To fill this gap, we used the DMSXL mouse model to study different brain cells by multiple omics approaches.
Methods: Cells were isolated from cortex of DMSXL/WT littermates, grown and differentiated to obtain homogenous cultures of primary neurons, astrocytes, oligodendrocyte precursor cells and mature oligodendrocytes. RNA samples were analyzed by RNA-Seq to characterize changes in alternative splicing and total gene expression. Total protein and phosphorylation levels were determined by mass spectrometry.
Results:
RNA-Seq analysis identified new splicing abnormalities in DMSXL brain cells. Gene expression was computed together with (phospho-)proteomics to gain an understanding of the pathways affected in each cell type.
Conclusion: Our analysis reveals the importance of combining multiple omics approaches in different CNS cells to shed new light on the pathways affected and provide an integrative view of DM1 brain dysfunction.