{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86663"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86663","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Regulating Endodermal Cell Lineage Through Genetic Manipulation of Developmental Regulatory Gene Circuits (DRGC's)","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Warren, Iyan; 0000-0002-0455-1390"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Parashurama, Natesh","Chemical and Biological Engineering"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-21T21:36:13Z","date_published":"2025-02-21T21:36:13Z","updated_at":"2026-07-27T19:05:34Z","subjects":["bioengineering","developmental biology","genetics"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/86663","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Parashurama, Natesh","Chemical and Biological Engineering"]},{"key":"dc:creator","label":"Author","values":["Warren, Iyan; 0000-0002-0455-1390"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-21T21:36:13Z","2020"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["bioengineering","developmental biology","genetics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/86663"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","Human Pluripotent stem cells (hPSC's) are a very useful tool for regenerative medicine allowing for the replacement of damaged tissues by implantation of functional tissue or cells. Of specific interest is the ability to properly differentiate liver, pancreas, and lung cells which all derive from endoderm using hPSC's. One issue that arises, is a result from the heterogeneity in the gene expression of hPSC-derived endoderm which can severely compromise the downstream fate of differentiation. Improper differentiation protocols of embryonic stem cells have also been shown to produce unwanted tissue during transplants including skeletal muscle, bone cell subpopulations, gut epithelial-like structures and columnar cells. Hepatocyte Nuclear Factor 3b (Foxa2) is known as a Pioneer Transcription Factor (TF) due to its ability to bind albumin enhancers and open normally inaccessible heterochromatin, effectively priming such for a cascade of regulatory elements to further differentiation through necessary gene activation. Foxa2 has been shown to be required for developmental processes such as transitioning to air breathing at birth, differentiation of pancreatic a-cells, and control of differentiation of goblet and enteroendocrine cells in mice. In combination with Foxa2, Hepatocyte Nuclear Factor 3a (Foxa1) has been shown to equally vital. Using this knowledge, we attempt to show that de-differentiation of HepG2 cells may be possible when these cells are no longer under the control of these pioneer transcription factors. Aside from this we attempt to show that the knockdown of these key liver factors will allow us to hold our differentiating stem cells in an endodermal like state by blocking signaling pathways, in hopes of better studying what transcription factors are important in a more homogeneous endoderm population.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulating Endodermal Cell Lineage Through Genetic Manipulation of Developmental Regulatory Gene Circuits (DRGC's)"]}]}],"canonical_facts":{"dc:contributor":["Parashurama, Natesh","Chemical and Biological Engineering"],"dc:creator":["Warren, Iyan; 0000-0002-0455-1390"],"dc:date":["2025-02-21T21:36:13Z","2020"],"dc:description":["M.S.","Human Pluripotent stem cells (hPSC's) are a very useful tool for regenerative medicine allowing for the replacement of damaged tissues by implantation of functional tissue or cells. Of specific interest is the ability to properly differentiate liver, pancreas, and lung cells which all derive from endoderm using hPSC's. One issue that arises, is a result from the heterogeneity in the gene expression of hPSC-derived endoderm which can severely compromise the downstream fate of differentiation. Improper differentiation protocols of embryonic stem cells have also been shown to produce unwanted tissue during transplants including skeletal muscle, bone cell subpopulations, gut epithelial-like structures and columnar cells. Hepatocyte Nuclear Factor 3b (Foxa2) is known as a Pioneer Transcription Factor (TF) due to its ability to bind albumin enhancers and open normally inaccessible heterochromatin, effectively priming such for a cascade of regulatory elements to further differentiation through necessary gene activation. Foxa2 has been shown to be required for developmental processes such as transitioning to air breathing at birth, differentiation of pancreatic a-cells, and control of differentiation of goblet and enteroendocrine cells in mice. In combination with Foxa2, Hepatocyte Nuclear Factor 3a (Foxa1) has been shown to equally vital. Using this knowledge, we attempt to show that de-differentiation of HepG2 cells may be possible when these cells are no longer under the control of these pioneer transcription factors. Aside from this we attempt to show that the knockdown of these key liver factors will allow us to hold our differentiating stem cells in an endodermal like state by blocking signaling pathways, in hopes of better studying what transcription factors are important in a more homogeneous endoderm population.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86663"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["bioengineering","developmental biology","genetics"],"dc:title":["Regulating Endodermal Cell Lineage Through Genetic Manipulation of Developmental Regulatory Gene Circuits (DRGC's)"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:34Z"}