Abstract
Human neurodegenerative diseases arise from the interplay of genetic perturbations, cellular identity, and age-associated stress pathways. A major barrier to dissecting these mechanisms is the lack of human-relevant neuronal models that retain patient-specific and age-associated molecular signatures. This dissertation integrates two complementary lines of investigation that collectively establish direct neuronal reprogramming as a framework for revealing mechanistic vulnerability in human neurodegeneration. The first component of this work dissects the transcriptional and epigenetic logic by which human fibroblasts undergo stepwise conversion into neurons through microRNA-mediated reprogramming. By defining the intermediate cell states and regulatory checkpoints that govern identity erasure and neuronal acquisition, this published study provides a mechanistic foundationfor generating mature, age-relevant human neurons directly from patient cells. These findings demonstrate that microRNA-driven neuronal reprogramming preserves molecular features essential for modeling late-onset neurodegenerative disease.
Committee Chair
Andrew S. Yoo
Committee Members
Carlos Cruchaga, Harrison Gabel, Celeste Karch, Hiroko Yano
Degree
Doctor of Philosophy (PhD)
Author's Department
Biology & Biomedical Sciences (Computational & Systems Biology)
Document Type
Dissertation
Date of Award
12-15-2025
Language
English (en)
Recommended Citation
Kwon, Ji-Sun, "Mechanistic insights into human neuronal reprogramming and vulnerability in Huntington’s disease" (2025). Arts & Sciences Theses and Dissertations. 3697.
https://openscholarship.wustl.edu/art_sci_etds/3697