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Hypoxia and Chromatin Remodeling: Essential Regulators of Ocular Lens Cell Differentiation

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Date Issued:
2022
Abstract/Description:
The ocular lens is comprised of an epithelial cell population that undergoes a continuous process of cellular remodeling and differentiation to form elongated transparent fiber cells. This lens differentiation process is hallmarked by the complete elimination of organelles at the center of the lens, elongation of lens fiber cells, and production of lens fiber-cell specific crystallin proteins to form the mature functional structure of the transparent ocular lens. To date, our understanding of the mechanisms that drive the lens differentiation process is incomplete. This dissertation sought to elucidate the potential roles of both hypoxia and epigenetic chromatin remodeling processes as novel regulators of lens differentiation. The lens lacks a direct blood supply and thus resides in a hypoxic microenvironment. Previous studies revealed the presence of a decreasing oxygen gradient in the region of the lens where cellular remodeling and organelle elimination occur to form mature transparent lens fiber cells. Thus we hypothesized that the hypoxic environment of the lens itself, was required to induce gene expression changes to drive the lens differentiation process. We utilized a multimoics analysis combining CUT&RUN and RNAseq high-throughput sequencing technologies to identify a role for the hypoxia-inducible transcription factor HIF1a as a novel regulator of lens gene expression during lens differentiation.
Title: Hypoxia and Chromatin Remodeling: Essential Regulators of Ocular Lens Cell Differentiation.
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Name(s): Disatham, Joshua , author
Kantorow, Marc , Thesis advisor
Florida Atlantic University, Degree grantor
Department of Biological Sciences
Charles E. Schmidt College of Science
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2022
Date Issued: 2022
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 221 p.
Language(s): English
Abstract/Description: The ocular lens is comprised of an epithelial cell population that undergoes a continuous process of cellular remodeling and differentiation to form elongated transparent fiber cells. This lens differentiation process is hallmarked by the complete elimination of organelles at the center of the lens, elongation of lens fiber cells, and production of lens fiber-cell specific crystallin proteins to form the mature functional structure of the transparent ocular lens. To date, our understanding of the mechanisms that drive the lens differentiation process is incomplete. This dissertation sought to elucidate the potential roles of both hypoxia and epigenetic chromatin remodeling processes as novel regulators of lens differentiation. The lens lacks a direct blood supply and thus resides in a hypoxic microenvironment. Previous studies revealed the presence of a decreasing oxygen gradient in the region of the lens where cellular remodeling and organelle elimination occur to form mature transparent lens fiber cells. Thus we hypothesized that the hypoxic environment of the lens itself, was required to induce gene expression changes to drive the lens differentiation process. We utilized a multimoics analysis combining CUT&RUN and RNAseq high-throughput sequencing technologies to identify a role for the hypoxia-inducible transcription factor HIF1a as a novel regulator of lens gene expression during lens differentiation.
Identifier: FA00013985 (IID)
Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2022.
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Includes bibliography.
Subject(s): Hypoxia
Chromatin
Cell Differentiation
Eye
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00013985
Use and Reproduction: Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
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Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.