Date of Award
8-1-2024
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Understanding the mechanisms that underlie cell fate and status decisions remains a complex task in biological research. Despite sharing identical genetic content, cells can differentiate into diverse types or remain in different statuses based on epigenetic dynamics. Here, I have structured my thesis into two distinct but interconnected parts, each focusing on a specific aspect of epigenetic control during zebrafish development and regeneration. The first part of the thesis focuses on the differentiation of pigment cells from neural crest cells to understand how the same progenitor cell population can bifurcate into two different pigment cell lineages. Through a comprehensive analysis of DNA methylation, chromatin accessibility, and transcriptome datasets from early and late neural crest cells, as well as in differentiated melanophore and iridophore cells at around 5 days post-fertilization, this study uncovers the dynamic epigenetic landscape that shapes cell-type-specific gene expression. We discovered significant DNA demethylation events and chromatin accessibility variations that facilitate regulatory control over gene expression. Moreover, motif enrichment analysis in epigenetically dynamic regions demonstrated that alx4a is an essential transcription factor for iridophore differentiation, further elucidating its potential regulatory role in the guanine synthesis pathway, which is crucial for pigment production. The second part of the thesis leverages single-nucleus sequencing technology to chart the chromatin accessibility and transcriptomic landscapes during zebrafish caudal fin regeneration at single-nucleus resolution. This approach provides a view of the regulatory dynamics governing cellular status changes. Our findings reveal a marked increase in chromatin accessibility linked to regenerative and developmental genes early post-injury, followed by a gradual closure of these regions in major cell types at subsequent stages. This detailed landscape revealed several waves of gene regulation and allowed the identification of cell type-specific and position-specific enhancers active in regeneration. By constructing regulatory networks based on cell type and regeneration stage, the study provides novel insights into the complex regulatory mechanisms of regeneration, contributing valuable knowledge to the field. By combining these two research areas, this thesis not only sheds light on the intricate processes of cell fate determination and regeneration from an epigenetic perspective but also offers a comprehensive resource for further exploration of epigenetic regulation in zebrafish pigment development and caudal fin regeneration processes.
Language
English (en)
Chair and Committee
Ting Wang
Committee Members
Benjamin Humphreys; Douglas Chalker; Guoyan Zhao; Mayssa Mokalled
Recommended Citation
Chen, Yujie, "Epigenetic Dynamics in Zebrafish Development and Regeneration" (2024). Arts & Sciences Electronic Theses and Dissertations. 3288.
https://openscholarship.wustl.edu/art_sci_etds/3288