{"id":{"repo_id":"missouri","oai_identifier":"oai:mospace.umsystem.edu:10355/108948"},"canonical_url":"https://search.dev.ndltd.org/etd/missouri/oai:mospace.umsystem.edu:10355/108948","repository":{"repo_id":"missouri","name":"University of Missouri","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"Exogenous donor-derived hepatogenesis in chimeric hosts","abstract":"This dissertation investigates advanced genetic engineering techniques and the creation of intra- and interspecies chimeras to explore liver development and the potential for generating donor-derived organs in chimeric hosts. In this dissertation, we begin with a comprehensive review of the literature (Chapter I) regarding histology and anatomy of liver, cardinal functions of the liver, followed by an overview of the current knowledge of embryonic liver development with a specific focus on molecular pathways and genes crucial for hepatogenesis. Specific focus was given to gatekeepr genes such as Foxa, Gata, and Hhex. We also highlight the role of Fah in maintaining liver homeostasis. Additionally, a generalized introduction to advanced genome editing techniques was provided. In Chapter II, we outlined optimized strategies for generating Hhex and Fah knockout embryos using CRISPR/Cas9 and base editing techniques. The outlined methods tested the latest genetic engineering techniques and demonstrated the feasibility of generating successful gene knockouts with improved precision and consistency. This establishes a foundation for creating reliable models to study organogenesis and embryonic development in the context of liver formation. In Chapter III, intra- and interspecies chimeras were then generated by using pluripotent stem cells and blastocyst complementation to assess the integration and functionality of donor-derived liver cells in the host embryos. Our findings reveal both the potential and limitations of intra and intererspecies chimerism in overcoming developmental barriers and achieving successful organogenesis. Building on these results, blastocyst complementation experiments were conducted in a large animal biomedical pig model lacking liver development (ahepatic pigs), successfully generating donor-derived liver tissues. Final Chapter was dedicated to summarize our current findings and a discussion on future directions to enhance the efficiency of generating exogenous organs. Taken together, this body of work is expected to advance our current understanding of the field of regenerative medicine by providing insights into the development of functional, donor-derived organs in chimeric hosts.","abstract_html":"This dissertation investigates advanced genetic engineering techniques and the creation of intra- and interspecies chimeras to explore liver development and the potential for generating donor-derived organs in chimeric hosts. In this dissertation, we begin with a comprehensive review of the literature (Chapter I) regarding histology and anatomy of liver, cardinal functions of the liver, followed by an overview of the current knowledge of embryonic liver development with a specific focus on molecular pathways and genes crucial for hepatogenesis. Specific focus was given to gatekeepr genes such as Foxa, Gata, and Hhex. We also highlight the role of Fah in maintaining liver homeostasis. Additionally, a generalized introduction to advanced genome editing techniques was provided. In Chapter II, we outlined optimized strategies for generating Hhex and Fah knockout embryos using CRISPR/Cas9 and base editing techniques. The outlined methods tested the latest genetic engineering techniques and demonstrated the feasibility of generating successful gene knockouts with improved precision and consistency. This establishes a foundation for creating reliable models to study organogenesis and embryonic development in the context of liver formation. In Chapter III, intra- and interspecies chimeras were then generated by using pluripotent stem cells and blastocyst complementation to assess the integration and functionality of donor-derived liver cells in the host embryos. Our findings reveal both the potential and limitations of intra and intererspecies chimerism in overcoming developmental barriers and achieving successful organogenesis. Building on these results, blastocyst complementation experiments were conducted in a large animal biomedical pig model lacking liver development (ahepatic pigs), successfully generating donor-derived liver tissues. Final Chapter was dedicated to summarize our current findings and a discussion on future directions to enhance the efficiency of generating exogenous organs. Taken together, this body of work is expected to advance our current understanding of the field of regenerative medicine by providing insights into the development of functional, donor-derived organs in chimeric hosts.","abstract_has_math":false,"creators":["Yeddula, Sai Goutham Reddy"],"institution":"University of Missouri--Columbia","degree_name":"Ph. D.","degree_level":"Doctoral","degree_discipline":"Animal sciences (MU)","degree_department":null,"school":null,"contributors":[],"advisors":["Telugu, Bhanu"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024","date_published":"2024","updated_at":"2026-07-24T03:09:27Z","subjects":[],"languages":["eng","English"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.32469/10355/108948"],"render_values":[{"text":"https://doi.org/10.32469/10355/108948","href":"https://doi.org/10.32469/10355/108948","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10355/108948","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Telugu, Bhanu"]},{"key":"dc:creator","label":"Author","values":["Yeddula, Sai Goutham Reddy"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-03T14:04:35Z"]},{"key":"dc:date.issued","label":"Date","values":["2024"]},{"key":"dc:publisher","label":"Institution","values":["University of Missouri--Columbia"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Animal sciences (MU)"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. 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In this dissertation, we begin with a comprehensive review of the literature (Chapter I) regarding histology and anatomy of liver, cardinal functions of the liver, followed by an overview of the current knowledge of embryonic liver development with a specific focus on molecular pathways and genes crucial for hepatogenesis. Specific focus was given to gatekeepr genes such as Foxa, Gata, and Hhex. We also highlight the role of Fah in maintaining liver homeostasis. Additionally, a generalized introduction to advanced genome editing techniques was provided. In Chapter II, we outlined optimized strategies for generating Hhex and Fah knockout embryos using CRISPR/Cas9 and base editing techniques. The outlined methods tested the latest genetic engineering techniques and demonstrated the feasibility of generating successful gene knockouts with improved precision and consistency. This establishes a foundation for creating reliable models to study organogenesis and embryonic development in the context of liver formation. In Chapter III, intra- and interspecies chimeras were then generated by using pluripotent stem cells and blastocyst complementation to assess the integration and functionality of donor-derived liver cells in the host embryos. Our findings reveal both the potential and limitations of intra and intererspecies chimerism in overcoming developmental barriers and achieving successful organogenesis. Building on these results, blastocyst complementation experiments were conducted in a large animal biomedical pig model lacking liver development (ahepatic pigs), successfully generating donor-derived liver tissues. Final Chapter was dedicated to summarize our current findings and a discussion on future directions to enhance the efficiency of generating exogenous organs. Taken together, this body of work is expected to advance our current understanding of the field of regenerative medicine by providing insights into the development of functional, donor-derived organs in chimeric hosts."]},{"key":"dc:title","label":"Title","values":["Exogenous donor-derived hepatogenesis in chimeric hosts"]}]}],"canonical_facts":{"dc:contributor.advisor":["Telugu, Bhanu"],"dc:creator":["Yeddula, Sai Goutham Reddy"],"dc:date.accessioned":["2025-07-03T14:04:35Z"],"dc:date.issued":["2024"],"dc:description.abstract":["This dissertation investigates advanced genetic engineering techniques and the creation of intra- and interspecies chimeras to explore liver development and the potential for generating donor-derived organs in chimeric hosts. In this dissertation, we begin with a comprehensive review of the literature (Chapter I) regarding histology and anatomy of liver, cardinal functions of the liver, followed by an overview of the current knowledge of embryonic liver development with a specific focus on molecular pathways and genes crucial for hepatogenesis. Specific focus was given to gatekeepr genes such as Foxa, Gata, and Hhex. We also highlight the role of Fah in maintaining liver homeostasis. Additionally, a generalized introduction to advanced genome editing techniques was provided. In Chapter II, we outlined optimized strategies for generating Hhex and Fah knockout embryos using CRISPR/Cas9 and base editing techniques. The outlined methods tested the latest genetic engineering techniques and demonstrated the feasibility of generating successful gene knockouts with improved precision and consistency. This establishes a foundation for creating reliable models to study organogenesis and embryonic development in the context of liver formation. In Chapter III, intra- and interspecies chimeras were then generated by using pluripotent stem cells and blastocyst complementation to assess the integration and functionality of donor-derived liver cells in the host embryos. Our findings reveal both the potential and limitations of intra and intererspecies chimerism in overcoming developmental barriers and achieving successful organogenesis. Building on these results, blastocyst complementation experiments were conducted in a large animal biomedical pig model lacking liver development (ahepatic pigs), successfully generating donor-derived liver tissues. Final Chapter was dedicated to summarize our current findings and a discussion on future directions to enhance the efficiency of generating exogenous organs. Taken together, this body of work is expected to advance our current understanding of the field of regenerative medicine by providing insights into the development of functional, donor-derived organs in chimeric hosts."],"dc:identifier.doi":["https://doi.org/10.32469/10355/108948"],"dc:identifier.uri":["https://hdl.handle.net/10355/108948"],"dc:language":["English"],"dc:language.iso":["eng"],"dc:publisher":["University of Missouri--Columbia"],"dc:title":["Exogenous donor-derived hepatogenesis in chimeric hosts"],"dc:type":["Thesis"],"thesis:degree_discipline":["Animal sciences (MU)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["University of Missouri--Columbia"]},"updated_at":"2026-07-24T03:09:27Z"}