Alternative splicing control over naïve and primed pluripotency

[eng] A fundamental step in embryo development is the transition through pluripotency. There are two known sequential states of pluripotency termed naïve and primed pluripotency. Considerable efforts have been made to characterize these two cell identities using gene expression, protein, metabolic a...

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Detalles Bibliográficos
Autor: Rodríguez Vaello, Victoria Eugenia
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/179434
Acceso en línea:https://hdl.handle.net/2445/179434
http://hdl.handle.net/10803/672261
Access Level:acceso abierto
Palabra clave:Genòmica
Biologia del desenvolupament
Cèl·lules mare
Genomics
Developmental biology
Stem cells
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spelling Alternative splicing control over naïve and primed pluripotencyRodríguez Vaello, Victoria EugeniaGenòmicaBiologia del desenvolupamentCèl·lules mareGenomicsDevelopmental biologyStem cells[eng] A fundamental step in embryo development is the transition through pluripotency. There are two known sequential states of pluripotency termed naïve and primed pluripotency. Considerable efforts have been made to characterize these two cell identities using gene expression, protein, metabolic and epigenetic profiling; here we explore an additional regulatory layer, at the level of alternative pre-mRNA splicing (AS). We performed deep coverage RNA sequencing on embryo-derived stem cell lines and identified a regulated AS landscape between the two states involving over 900 splicing events. These events show distinct cis-regulatory features and can also be observed in vivo and in the equivalent human pluripotency states. Differential gene expression analyses helped to identify two regulatory axes that contribute to shape these AS landscapes: the Rbmx/RbmxL2 and the Rbm47/Esrp axes. We further performed a high-throughput screen to test the effect of 1,500 single knockdowns of RNA binding proteins and chromatin modifiers on naïve-to-primed AS switches. This led us to the identification of Qki as an additional master naïve-to-primed AS regulator. Functional assays show that depletion of these splicing regulators affect the differentiation dynamics of embryonic stem cells. Overall, our results provide new insights into the regulatory programs governing naïve and primed pluripotency and the gain of differentiation potential.Universitat de BarcelonaIrimia Martínez, ManuelUniversitat de Barcelona. Facultat de Biologia2020info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/179434http://hdl.handle.net/10803/672261Tesis Doctorals - Facultat - Biologiareponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Rodríguez Vaello, Victoria Eugenia, 2021info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1794342026-05-27T06:46:51Z
dc.title.none.fl_str_mv Alternative splicing control over naïve and primed pluripotency
title Alternative splicing control over naïve and primed pluripotency
spellingShingle Alternative splicing control over naïve and primed pluripotency
Rodríguez Vaello, Victoria Eugenia
Genòmica
Biologia del desenvolupament
Cèl·lules mare
Genomics
Developmental biology
Stem cells
title_short Alternative splicing control over naïve and primed pluripotency
title_full Alternative splicing control over naïve and primed pluripotency
title_fullStr Alternative splicing control over naïve and primed pluripotency
title_full_unstemmed Alternative splicing control over naïve and primed pluripotency
title_sort Alternative splicing control over naïve and primed pluripotency
dc.creator.none.fl_str_mv Rodríguez Vaello, Victoria Eugenia
author Rodríguez Vaello, Victoria Eugenia
author_facet Rodríguez Vaello, Victoria Eugenia
author_role author
dc.contributor.none.fl_str_mv Irimia Martínez, Manuel
Universitat de Barcelona. Facultat de Biologia
dc.subject.none.fl_str_mv Genòmica
Biologia del desenvolupament
Cèl·lules mare
Genomics
Developmental biology
Stem cells
topic Genòmica
Biologia del desenvolupament
Cèl·lules mare
Genomics
Developmental biology
Stem cells
description [eng] A fundamental step in embryo development is the transition through pluripotency. There are two known sequential states of pluripotency termed naïve and primed pluripotency. Considerable efforts have been made to characterize these two cell identities using gene expression, protein, metabolic and epigenetic profiling; here we explore an additional regulatory layer, at the level of alternative pre-mRNA splicing (AS). We performed deep coverage RNA sequencing on embryo-derived stem cell lines and identified a regulated AS landscape between the two states involving over 900 splicing events. These events show distinct cis-regulatory features and can also be observed in vivo and in the equivalent human pluripotency states. Differential gene expression analyses helped to identify two regulatory axes that contribute to shape these AS landscapes: the Rbmx/RbmxL2 and the Rbm47/Esrp axes. We further performed a high-throughput screen to test the effect of 1,500 single knockdowns of RNA binding proteins and chromatin modifiers on naïve-to-primed AS switches. This led us to the identification of Qki as an additional master naïve-to-primed AS regulator. Functional assays show that depletion of these splicing regulators affect the differentiation dynamics of embryonic stem cells. Overall, our results provide new insights into the regulatory programs governing naïve and primed pluripotency and the gain of differentiation potential.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/179434
http://hdl.handle.net/10803/672261
url https://hdl.handle.net/2445/179434
http://hdl.handle.net/10803/672261
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Rodríguez Vaello, Victoria Eugenia, 2021
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Rodríguez Vaello, Victoria Eugenia, 2021
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Biologia
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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