{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10447"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10447","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Regulation of Liver Homeostasis and Regeneration","abstract":"The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","abstract_html":"The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","abstract_has_math":false,"creators":["Lin, Yu-Hsuan"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Tagliabracci, Vincent S.","Zhu, Hao","Olson, Eric N.","O'Donnell, Kathryn A."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-01-02T21:57:50Z","date_published":"2025-01-02T21:57:50Z","updated_at":"2026-07-24T05:52:36Z","subjects":["Hepatocytes","Homeostasis","Liver","Liver Regeneration","Polyploidy"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1482732349"],"render_values":[{"text":"1482732349","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10447","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Tagliabracci, Vincent S.","Zhu, Hao","Olson, Eric N.","O'Donnell, Kathryn A."]},{"key":"dc:creator","label":"Author","values":["Lin, Yu-Hsuan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-01-02T21:57:50Z","2022-12","December 2022"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Hepatocytes","Homeostasis","Liver","Liver Regeneration","Polyploidy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10447","1482732349"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","Although hepatocytes and biliary epithelial cells are slow-cycling during normal homeostasis, liver tissue is remarkably regenerative, and can quickly proliferate to recover from injury. However, this regenerative capacity is often dysregulated in chronic liver diseases and liver cancer. Understanding the regulation of liver homeostasis and regeneration will provide solid scientific ground to develop therapies for patients. The first part of the thesis was to investigate two unique characteristics that cause cellular heterogeneity in the liver, hepatic zonation and polyploidy, under liver homeostasis and regeneration. To determine whether the zonal heterogeneity leads to differences in regenerative capacity, the Igfbp2-CreER line was generated to lineage trace midlobular hepatocytes. The results showed that the midlobular cells preferentially contribute to tissue maintenance and regeneration. The liver is also known for a high percentage of polyploid cells. To investigate its functional roles, the inducible Anln knockdown mouse model was used to induce hepatic ploidy. In super-polyploid mice with 97% polyploid hepatocytes, the regenerative capacity, tissue fitness, gene regulation and mitotic errors were unchanged. Moreover, the mice were substantially protected from tumorigenesis induced by mutagen and chronic liver injuries. The second goal of my thesis is to identify secreted growth regulators of regeneration. I used in vivo CRISPR knockout screening to identify Secreted Phosphoprotein 2 (SPP2) as a negative regulator of liver regeneration. Spp2 loss-of-function mice showed protection against acute liver failure but also against chronic fatty liver disease and chemically induced fibrosis. Biochemical studies revealed multiple candidate interaction partners for Spp2, and among these, integrins are potential mediators of some Spp2 phenotypes. Altogether, this study offers new ways to discover, validate, and characterize secreted factors."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulation of Liver Homeostasis and Regeneration"]}]}],"canonical_facts":{"dc:contributor":["Tagliabracci, Vincent S.","Zhu, Hao","Olson, Eric N.","O'Donnell, Kathryn A."],"dc:creator":["Lin, Yu-Hsuan"],"dc:date":["2025-01-02T21:57:50Z","2022-12","December 2022"],"dc:description":["The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","Although hepatocytes and biliary epithelial cells are slow-cycling during normal homeostasis, liver tissue is remarkably regenerative, and can quickly proliferate to recover from injury. However, this regenerative capacity is often dysregulated in chronic liver diseases and liver cancer. Understanding the regulation of liver homeostasis and regeneration will provide solid scientific ground to develop therapies for patients. The first part of the thesis was to investigate two unique characteristics that cause cellular heterogeneity in the liver, hepatic zonation and polyploidy, under liver homeostasis and regeneration. To determine whether the zonal heterogeneity leads to differences in regenerative capacity, the Igfbp2-CreER line was generated to lineage trace midlobular hepatocytes. The results showed that the midlobular cells preferentially contribute to tissue maintenance and regeneration. The liver is also known for a high percentage of polyploid cells. To investigate its functional roles, the inducible Anln knockdown mouse model was used to induce hepatic ploidy. In super-polyploid mice with 97% polyploid hepatocytes, the regenerative capacity, tissue fitness, gene regulation and mitotic errors were unchanged. Moreover, the mice were substantially protected from tumorigenesis induced by mutagen and chronic liver injuries. The second goal of my thesis is to identify secreted growth regulators of regeneration. I used in vivo CRISPR knockout screening to identify Secreted Phosphoprotein 2 (SPP2) as a negative regulator of liver regeneration. Spp2 loss-of-function mice showed protection against acute liver failure but also against chronic fatty liver disease and chemically induced fibrosis. Biochemical studies revealed multiple candidate interaction partners for Spp2, and among these, integrins are potential mediators of some Spp2 phenotypes. Altogether, this study offers new ways to discover, validate, and characterize secreted factors."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10447","1482732349"],"dc:language":["en"],"dc:subject":["Hepatocytes","Homeostasis","Liver","Liver Regeneration","Polyploidy"],"dc:title":["Regulation of Liver Homeostasis and Regeneration"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:36Z"}