Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de Lectura: 08-07-2022

Detalles Bibliográficos
Autor: García González, Irene
Tipo de recurso: tesis doctoral
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/704162
Acceso en línea:http://hdl.handle.net/10486/704162
Access Level:acceso abierto
Palabra clave:Biociencias Moleculares
Biología y Biomedicina / Biología
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spelling Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesisGarcía González, IreneBiociencias MolecularesBiología y Biomedicina / BiologíaTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de Lectura: 08-07-2022Esta Tesis tiene embargado el acceso al texto completo hasta el 08-01-2024Recombinase genetic tools are extensively used in biomedical research to label cells and tissues or to modify the genotype of a cell and are very useful to understand development and disease progression. There are recombinase-reporters that allow us to label specific tissues/cell-types; there are floxed lines that allow us to induce deletion of genes; and driver lines that induce the expression of recombinases to delete a gene or recombine a reporter only in the tissue of interest and at a specific time point. These lines are powerful tools when combined but, as we describe in the first chapter of this thesis, can caused misinterpretation of results if misused. We show here why Cre-reporters should not be used as indicators of gene deletion and present a new set of ratiometric multispectral mosaic genetic tools, called iFlp-Mosaics¸ as an alternative for reliable KO and WT labelling of cells, which will be of broad interest for the research community. In the second part of this thesis we apply iFlp-Mosaics as well as classical genetic tools, to understand the role of polyamines in cellular competition and segregation during angiogenesis. Polyamines are small cationic peptides synthesised by ODC1 enzyme and are implicated in several cellular processes such as proliferation and migration which are important for angiogenesis. Thanks to the iFlp-Mosaics we can study how different cell types respond to mosaic Odc1 deletion. While some cell types are capable of adapting and compensating over time others cell types cannot adapt and KO cells are outcompeted by WT cells. We demonstrate how this compensation in endothelial cells (ECs) could be driven by import of polyamines from extracellular sources and how cells with abnormally low or high levels of polyamines, despite their competitive nature, behave different when they are not in a mosaic situation. Finally, we also compare the deletion of Odc1 with the deletion of its direct activator c-Myc, both negatively regulated by Notch in angiogenesis, and find that deletion of c-Myc is in most cases not as easy to compensate by the cells as Odc1Benedito, RuiDepartamento de BioquímicaFacultad de MedicinaCentro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)20222022-07-08doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/704162reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7041622026-06-23T12:46:27Z
dc.title.none.fl_str_mv Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis
title Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis
spellingShingle Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis
García González, Irene
Biociencias Moleculares
Biología y Biomedicina / Biología
title_short Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis
title_full Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis
title_fullStr Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis
title_full_unstemmed Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis
title_sort Using genetic mosaics to understand the role of polyamine biosynthesis in cellular competition and segregation during angiogenesis
dc.creator.none.fl_str_mv García González, Irene
author García González, Irene
author_facet García González, Irene
author_role author
dc.contributor.none.fl_str_mv Benedito, Rui
Departamento de Bioquímica
Facultad de Medicina
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
dc.subject.none.fl_str_mv Biociencias Moleculares
Biología y Biomedicina / Biología
topic Biociencias Moleculares
Biología y Biomedicina / Biología
description Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de Lectura: 08-07-2022
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-07-08
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/704162
url http://hdl.handle.net/10486/704162
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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