Abstract

Neurogenic differentiation requires coordinated redox regulation, yet how reversible cysteine oxidation is remodeled at proteome scale during this process remains poorly defined. Here, we asked whether differentiation is associated with selective, site-specific changes in reversible cysteine oxidation and whether oxidative stress reveals developmentally conditioned vulnerabilities within this redox landscape. To address this, we applied a discovery-oriented, proteome-scale redox profiling strategy that quantifies condition-dependent changes in reversible cysteine oxidation using CysPAT labeling, phosphopeptide enrichment, and multiplexed TMT mass spectrometry. Neurogenic differentiation was characterized by reproducible, bidirectional, and highly site-specific remodeling of reversible cysteine oxidation at discrete regulatory nodes, as well as a larger subset cysteine sites that did not change oxidation states due to neurogenesis. Differentially oxidized cysteine sites were distributed across major pathways relevant to neurogenesis, including translational control and ribosome biogenesis, central carbon metabolism and metabolic rewiring, nuclear and chromatin-associated regulation, redox homeostasis and antioxidant systems, cell-cycle control, and developmental/neurogenic signaling pathways. Acute oxidative stress induced by paraquat elicited strong but selective redox responses in both undifferentiated and differentiated cells, yet the majority of cysteine sites remained unchanged. Although global stress signatures were broadly conserved between cell states, site-level analyses revealed pronounced, developmentally conditioned differences in cysteine susceptibility: undifferentiated cells exhibited greater dysregulation at developmentally tuned sites, whereas differentiated cells preferentially preserved established redox states under oxidative challenge. Together, these findings demonstrate that redox regulation of individual cysteine residues within key regulatory proteins constitutes a fundamental layer of developmental control, and that disruption of these site-specific redox programs provides a plausible molecular basis for oxidative stress"“induced dysmorphogenesis, impaired neurogenesis, and developmental toxicity.

Degree

MS

College and Department

Life Sciences; Cell Biology and Physiology

Rights

https://lib.byu.edu/about/copyright/

Date Submitted

2026-04-10

Document Type

Thesis

Keywords

neurogenesis, differentiation, development, redox proteome, oxidative stress, dysmorphogenesis, developmental toxicity

Language

english

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Life Sciences Commons

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