Analysis of Age and Sex-Specific Differences in Gene and pri-miRNA Expression in the Cell-Types of the Mus Musculus Subventricular Zone

Elias, Amy Elizabeth

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Year:: 2022
Contributor:: Elias, Amy Elizabeth (creator); Sedivy, John (Reader); Webb, Ashley (Reader); Freiman, Richard (Reader); Kreiling, Jill (Advisor); Suh, Yousin (Reader); Brown University. Department of Molecular Biology, Cell Biology and Biochemistry (sponsor)
Genre:: theses
Subject:: miRNA; Aging; Neural stem cells; single-nucleus sequencing; subventricular zone
Extent:: xvi, 237 p.

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Abstract:: Neurogenesis sharply declines with age in the subventricular zone (SVZ). The SVZ niche contains multipotent neural stem cells (NSCs) that can differentiate into neurons, astrocytes, or oligodendrocytes. With age, however, they decline in number and proliferative capability. The impact of gene expression changes in each cell type with age and the impact of sex-specific differences with age are unknown in the SVZ.. In addition to gene expression, regulatory RNA expression such as global microRNA (miRNA) expression, per cell-type, has not been explored in the aging SVZ. miRNAs contribute to gene regulation via translational repression or degradation of mRNAs. To analyze the changes in gene expression and miRNA expression, we created a reference for primary microRNA (pri-miRNA) sequences compatible with the 10X Genomics mm10 reference genome, and we used this to align single-nucleus sequencing data from young (3-4 month old) male and female mice as well as aged (25-26 month old) male and female mice. From this newly created “primiRreference”, we were able to profile changes in pri-miRNA expression with age and noted that most of the predicted genes of the miRNAs are part of pathways having to do with pathways determining NSC proliferation and differentiation. Therefore, it is likely these pri-miRNAs contribute to SVZ decline with age. Moreover, we noted that the female SVZ and male SVZ have great differences in gene expression in the young group while their expression of gene and pri-miRNAs becomes more similar with age. Many of these genes changing with age and predicted genes of pri-miRNAs have to do with calcium and Wnt signaling. Therefore, it is suggested that female and male SVZ cell-types have different control of these pathways leading to key differences in proliferation and differentiation in the young possibly leading to key differences in the aged populations.
Notes:: Thesis (Ph. D.)--Brown University, 2022

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Citation

Elias, Amy Elizabeth, "Analysis of Age and Sex-Specific Differences in Gene and pri-miRNA Expression in the Cell-Types of the Mus Musculus Subventricular Zone" (2022). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:u8acwz2c/

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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations

Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department.
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