Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects
[eng] The Central nervous system (CNS) originates from the coordinated events that result into neural specification and the morphogenic events that shape the neural tube (NT). Then, the embryonic NT should grow and generate all the cell diversity present in the healthy organ. The morphogenic events...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/196742 |
| Acceso en línea: | https://hdl.handle.net/2445/196742 http://hdl.handle.net/10803/688045 |
| Access Level: | acceso abierto |
| Palabra clave: | Sistema nerviós central Neurobiologia del desenvolupament Morfogènesi Central nervous system Developmental neurobiology Morphogenesis |
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Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects |
| title |
Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects |
| spellingShingle |
Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects Blanco Ameijeiras, Jose Manuel Sistema nerviós central Neurobiologia del desenvolupament Morfogènesi Central nervous system Developmental neurobiology Morphogenesis |
| title_short |
Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects |
| title_full |
Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects |
| title_fullStr |
Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects |
| title_full_unstemmed |
Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects |
| title_sort |
Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defects |
| dc.creator.none.fl_str_mv |
Blanco Ameijeiras, Jose Manuel |
| author |
Blanco Ameijeiras, Jose Manuel |
| author_facet |
Blanco Ameijeiras, Jose Manuel |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Martí Gorostiza, Elisa Universitat de Barcelona. Facultat de Biologia |
| dc.subject.none.fl_str_mv |
Sistema nerviós central Neurobiologia del desenvolupament Morfogènesi Central nervous system Developmental neurobiology Morphogenesis |
| topic |
Sistema nerviós central Neurobiologia del desenvolupament Morfogènesi Central nervous system Developmental neurobiology Morphogenesis |
| description |
[eng] The Central nervous system (CNS) originates from the coordinated events that result into neural specification and the morphogenic events that shape the neural tube (NT). Then, the embryonic NT should grow and generate all the cell diversity present in the healthy organ. The morphogenic events that shape the NT occur in two consecutive, radically different processes referred as primary and secondary neurulation, that can be followed at different anterio-posterior levels in the Spinal cord (SpC). The posterior NT is formed by secondary neurulation, in a process concomitant to body axis elongation and mediated by the specification of nueromesodermal progenitors (NMPs). Defects in this process lead to caudal neural tube defects (NTDs). In the first chapter of this thesis, a new human 3D in vitro model for posterior SpC is set up. In these human organoid models, the neural specification, the morphogenesis of the NT, and its grow can be followed. Here, it is characterized a human organoid model were human embryonic stem cells (hESC) are guided into NMPs, expressing SOX2 and BRA and then into neural progenitor cells (NPCs), which maintain the SOX2 and lose BRA expression as it happens in vivo. Moreover, the NPCs are organized as an epithelium surrounding a central lumen. NPCs locate the centrosome and cilia at the lumen surface, where the polarity complexes are organized mimicking the polarity features of NPCs characterized in vivo. Additionally, in parallel to this epithelialization, the cell rearranges that shape the hollow NT formation in vivo, like the cell intercalation driving lumen resolution, can be followed in this organoid model. In the second chapter of this thesis, a screening to identify new mature centrosome com- ponents that would be potentially control the NPCs proliferation/differentiation rates was done independently with an in vivo, using the chick embryo as model, and an in silico approach. Unfortunately, the in vivo approach faced technical limitations intrinsic of the chick embryo model that prevent any successful identification of new candidates. However, the in silico approach provided a list of candidates to start their functional analysis. |
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2023 |
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2023 |
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info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion |
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doctoralThesis |
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publishedVersion |
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https://hdl.handle.net/2445/196742 http://hdl.handle.net/10803/688045 |
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https://hdl.handle.net/2445/196742 http://hdl.handle.net/10803/688045 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
| dc.rights.none.fl_str_mv |
(c) Blanco Ameijeiras, Jose Manuel, 2023 info:eu-repo/semantics/openAccess |
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(c) Blanco Ameijeiras, Jose Manuel, 2023 |
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openAccess |
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application/pdf |
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Universitat de Barcelona |
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Universitat de Barcelona |
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Tesis Doctorals - Facultat - Biologia reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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1869412907781980160 |
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Building Human Spinal Cord Organoids (huSpineOrg) biomodels to study neural tube defectsBlanco Ameijeiras, Jose ManuelSistema nerviós centralNeurobiologia del desenvolupamentMorfogènesiCentral nervous systemDevelopmental neurobiologyMorphogenesis[eng] The Central nervous system (CNS) originates from the coordinated events that result into neural specification and the morphogenic events that shape the neural tube (NT). Then, the embryonic NT should grow and generate all the cell diversity present in the healthy organ. The morphogenic events that shape the NT occur in two consecutive, radically different processes referred as primary and secondary neurulation, that can be followed at different anterio-posterior levels in the Spinal cord (SpC). The posterior NT is formed by secondary neurulation, in a process concomitant to body axis elongation and mediated by the specification of nueromesodermal progenitors (NMPs). Defects in this process lead to caudal neural tube defects (NTDs). In the first chapter of this thesis, a new human 3D in vitro model for posterior SpC is set up. In these human organoid models, the neural specification, the morphogenesis of the NT, and its grow can be followed. Here, it is characterized a human organoid model were human embryonic stem cells (hESC) are guided into NMPs, expressing SOX2 and BRA and then into neural progenitor cells (NPCs), which maintain the SOX2 and lose BRA expression as it happens in vivo. Moreover, the NPCs are organized as an epithelium surrounding a central lumen. NPCs locate the centrosome and cilia at the lumen surface, where the polarity complexes are organized mimicking the polarity features of NPCs characterized in vivo. Additionally, in parallel to this epithelialization, the cell rearranges that shape the hollow NT formation in vivo, like the cell intercalation driving lumen resolution, can be followed in this organoid model. In the second chapter of this thesis, a screening to identify new mature centrosome com- ponents that would be potentially control the NPCs proliferation/differentiation rates was done independently with an in vivo, using the chick embryo as model, and an in silico approach. Unfortunately, the in vivo approach faced technical limitations intrinsic of the chick embryo model that prevent any successful identification of new candidates. However, the in silico approach provided a list of candidates to start their functional analysis.[spa] El desarrollo del sistema nervioso central (SNC) depende de la especificación del tejido neural y una serie de eventos morfogénicos que lo organizan en un tubo neural (NT). A partir de ahí, ese NT deberá crecer y generar toda la diversidad celular que presenta el órgano sano y le confiere su funcionalidad. Los eventos morfogénicos que dan forma al NT ocurren en dos procesos consecutivos radicalmente diferentes denominados neurulación primaria y secundaria, que pueden seguirse a diferentes niveles anteroposteriores en la médula espinal (SpC). El NT posterior se forma por neurulación secundaria, en un proceso simultáneo a la elongación del embrión y mediado por la especificación de progenitores nueromesodérmicos (NMP). Los defectos en este proceso conducen a defectos del tubo neural caudal (NTDs). En el primer capítulo de esta tesis, se establece in vitro un nuevo modelo 3D de SpC posterior humana. En estos organoides, se puede seguir la especificación neural, los procesos morfogenéticos de la formación del NT y su crecimiento. Aquí, se caracteriza un modelo de organoides humanos en el que las células madre embrionarias humanas (hESC) se guían hacia NMP, expresando SOX2 y BRA, que a continuación se diferencian en células progenitoras neurales (NPC). Estas últimas mantienen la SOX2 y pierden la expresión de BRA como sucede in vivo. Además, los NPC organizan un epitelio que rodea un único lumen central. Los NPC presentan su centrosoma y cilio en la superficie del lumen, donde los complejos de polaridad se organizan mimetizando las características de polaridad apical observadas in vivo. Además, en estos organoides se pueden seguir los reordenamientos celulares de los procesos morfogénicos que eventualmente forman un tubo neural hueco. En el segundo capítulo de esta tesis, se realizó un screening para identificar nuevos componentes de maduración del centrosoma que potencialmente controlarían el equilibrio de proliferación/diferenciación de los NPC. Este screening se realizó de forma independiente in vivo, utilizando el embrión de pollo como modelo, e in silico. Desafortunadamente, el enfoque in vivo enfrentó limitaciones técnicas intrínsecas del modelo que impidieron la identificación de nuevos candidatos. Sin embargo, el enfoque in silico proporcionó una lista de candidatos sobre los que comenzar un análisis funcional.Universitat de BarcelonaMartí Gorostiza, ElisaUniversitat de Barcelona. Facultat de Biologia2023info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/196742http://hdl.handle.net/10803/688045Tesis Doctorals - Facultat - Biologiareponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Blanco Ameijeiras, Jose Manuel, 2023info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1967422026-05-27T06:46:51Z |
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