Thesis
Modifying the epigenome to facilitate transdifferentiation of adult human skin fibroblasts
Master of Science (M.S.), Drexel University
Aug 2023
DOI:
https://doi.org/10.17918/00001807
Abstract
Recent advances in neuronal reprogramming have demonstrated that small molecule compounds can be used to directly convert human somatic cells, namely fibroblasts, into induced neurons (iNs). These small molecule compounds promote neuronal conversion while bypassing the neural progenitor stage by activating and repressing various pathways involved in differentiation; however, studies evaluating the possibility that pretreatments designed to modify the epigenome can facilitate neuronal reprogramming have not yet been conducted. Here, we report that pretreatment of human adult skin fibroblasts with demethylating agents 5-Azacytidine, 2'-deoxy-5-azacytidine, and p53 inhibitor Pifithrin-alpha directly prior to treatment with small molecule chemical cocktails facilitates modification of the epigenome of the cells and improves neuronal reprogramming efficiency in terms of morphological characteristics and protein expression profiles. As such, the demethylation-based pre-treatment approach discussed in this study makes an improvement on previously described protocols of neuronal reprogramming.
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Details
- Title
- Modifying the epigenome to facilitate transdifferentiation of adult human skin fibroblasts
- Creators
- Justin Do
- Contributors
- Christian Sell (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- viii, 58 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Medicine (Graduate); College of Medicine; Hematology and Oncology; Drexel University
- Other Identifier
- 991021229815604721