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Characterization of Genetically and Epigenetically Engineered Multicellular Systems and Their Application in Tissue Modeling and Hematopoiesis

LeGraw, Ryan Patrick (2024) Characterization of Genetically and Epigenetically Engineered Multicellular Systems and Their Application in Tissue Modeling and Hematopoiesis. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Pluripotent stem cell (PSC)-derived organoids have emerged as novel multicellular models of human tissue development but display can be difficult to rationally engineer, display immature phenotypes, and have been adopted in limited applications. Here, using our preciously established human induced pluripotent stem cell (hiPSC)- derived multilineage human liver organoids we develop tools for epigenetic engineering liver organoids, demonstrate integrated analysis and engineering of gene regulatory networks (GRNs) in PSC-derived multilineage human liver organoids to direct maturation and vascular morphogenesis in vitro through transcription factor engineering, and establish a model of hematopoietic stem cell (HSC) colonization and expansion in the human fetal liver as a platform for expansion of therapeutic HSCs. Collectively, our approach provides an experimental framework to guide epigenetic and genetic engineering of PSC-derived organoids for tissue modeling and novel therapeutic applications.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
LeGraw, Ryan Patrickryl17@pitt.eduryl170000-0002-5742-0706
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMars, WMwmars@pitt.eduWMARS
Thesis AdvisorEbrahimkhani, Momo.ebr@pitt.edu
Committee MemberKiani, Samirasamira.kiani@pitt.edu
Committee MemberDuncan, Andrewduncana@pitt.edu
Committee MemberBility, Mosesmtbility@pitt.edumtbility
Date: 16 September 2024
Date Type: Publication
Defense Date: 10 August 2023
Approval Date: 16 September 2024
Submission Date: 11 December 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 245
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Pathology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Organoid Liver hiPSC Stem cell Hematopoiesis
Date Deposited: 16 Sep 2024 18:51
Last Modified: 16 Sep 2024 18:51
URI: http://d-scholarship.pitt.edu/id/eprint/45649

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