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Application of human pluripotent stem cells and genetic engineering to treating and modeling pancreatic and cardiovascular degenerative diseases

Author
Jiang, Yuqian
Published
[University Park, Pennsylvania] : Pennsylvania State University, 2022.
Physical Description
1 electronic document
Additional Creators
Lian, Xiaojun
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Graduate Program
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Open Access.
Summary
Human pluripotent stem cells (hPSCs) hold unprecedented promise in providing unlimited cell sources for regenerative therapies, serving as versatile platforms for drug screening, disease modeling and understanding embryonic development. The combination with various genetic engineering tools unfolds acceleratively increasing applications. In this work, firstly I developed two genetically-modified hPSC models, which enables visualized characterization of hPSC-derived cardiomyocytes (hPSC-CMs). In addition, I established a robust growth-factor-free protocol named GiBi for generating definitive endoderm (DE) and pancreatic progenitor (PP) cells, facilitating scalable production of pancreatic cells for regenerative applications. Further optimization identified the culture medium and coating matrix compatible for our GiBi DE differentiation, enabling adaptation of this small-molecule-mediated DE protocol in different stem cell labs. Moreover, I investigated the possibility of forward programming of hPSCs or pancreatic progenitor cells into pancreatic [beta] cells via manipulation of transcription factors. Evidence was also provided for induced [beta] cell proliferation by activating Wnt signaling pathway. Last but not least, I developed several CRISPR-mediated systems, including two all-in-one PiggyBac vectors that can be utilized for genome or RNA editing in cell platforms and the Solid-State CRISPR-Cas12-Assisted Nanopores (SCAN) system for molecule detection.
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Dissertation Note
Ph.D. Pennsylvania State University 2022.
Technical Details
The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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