Cell Type-Specific Analysis of Bcl-xL Genomic Imprinting in the Mouse Brain
Ho-Shing, Olivia E.
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CitationHo-Shing, Olivia E. 2019. Cell Type-Specific Analysis of Bcl-xL Genomic Imprinting in the Mouse Brain. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractGenomic imprinting is a form of epigenetic inheritance that causes preferential expression of one allele based on its parent of origin. Imprinted expression plays crucial roles in brain development, and is associated with growth and mental disorders in humans including Prader-Willi and Angelman syndromes. Our lab has previously used RNA sequencing to uncover a large number of genes in the post-natal mouse brain, which exhibit a parental bias in their expression instead of canonical “all-or-none” imprinted expression. While these genes have been implicated in critical cellular pathways, it has been unclear what functional effects, if any, their biased expression may have on neuronal development and mature function. Moreover, we have no information about the nature of this biased expression at the level of individual neurons. Here, we investigate the gene Bcl2l1 (Bcl-xL), an anti-apoptotic regulator that exhibits a 60%:40% paternal bias in the cortex. We evaluate the functional consequences from brain-specific deletion of either the maternal or paternal allele of Bcl-x, using various cellular analyses and electrophysiological methods. We find that paternal, but not maternal deletion of Bcl-x affects cell survival and synaptic plasticity in the cortex. We also use single molecule fluorescence in situ hybridization to evaluate the nature of Bcl-xL biased expression at the level of single cells. Interestingly, we uncover remarkable cell type specificity to the imprinted expression of Bcl-xL in the cortex. Our findings shed new light on the impact of imprinted regulation on neuronal cell fate and function.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:42029525
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