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Multi-omics Assessment of Genomic Glucocorticoid Action in Murine Neural Stem and Progenitor Cells

Berry, Kimberly (2023) Multi-omics Assessment of Genomic Glucocorticoid Action in Murine Neural Stem and Progenitor Cells. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Prenatal exposure to synthetic glucocorticoids (sGCs) reprograms brain development and predisposes the developing fetus towards potential adverse neurodevelopmental outcomes. Using a mouse model of sGC administration, previous studies show that these changes are accompanied by sexually dimorphic alterations in the transcriptome of neural stem and progenitor cells (NSPCs) derived from the embryonic telencephalon. Because cell type-specific gene expression profiles tightly regulate cell fate decisions and are controlled by a flexible landscape of chromatin domains upon which transcription factors and enhancer elements act, we multiplexed data from four genome-wide assays: RNA-seq, ATAC-seq (assay for transposase accessible chromatin followed by genome wide sequencing), dual cross-linking ChIP-seq (chromatin immunoprecipitation followed by genome wide sequencing), and microarray gene expression to identify novel relationships between gene regulation, chromatin structure, and genomic glucocorticoid receptor (GR) action in NSPCs. These data reveal that GR binds preferentially to predetermined regions of accessible chromatin to influence gene programming and cell fate decisions. In addition, we identify SOX2 as a transcription factor that impacts the genomic response of select GR target genes to sGCs (i.e., dexamethasone) in NSPCs.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Berry, Kimberlykjb@pitt.edukjb
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee CoChairDeFranco, Donald Bdod1@pitt.edudod1
Committee CoChairSorrells,
Committee MemberLillien,
Committee MemberTorregrossa,
Committee MemberSeal,
Committee MemberSingh,
Date: 11 May 2023
Date Type: Publication
Defense Date: 27 February 2023
Approval Date: 11 May 2023
Submission Date: 3 April 2023
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 155
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Neural stem cell, glucocorticoid, chromatin, transcription
Date Deposited: 11 May 2023 14:44
Last Modified: 11 May 2023 14:44

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