Early autonomous patterning of the anteroposterior axis in gastruloids

Minimal in vitro systems composed of embryonic stem cells (ESCs) have been shown to recapitulate the establishment of the anteroposterior (AP) axis. In contrast to the native embryo, ESC aggregates – such as gastruloids – can break symmetry, which is demarcated by polarization of the mesodermal mark...

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Autores: Anlas, Kerim, Gritti, Nicola, Nakaki, Fumio, Salamó Palau, Laura, Tlili, Sham, Oriola Santandreu, David|||0000-0002-8356-7832, Arató, Krisztina, Lim, Jia Le, Sharpe, James, Trivedi, Vikas
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/423636
Acceso en línea:https://hdl.handle.net/2117/423636
https://dx.doi.org/10.1242/dev.202171
Access Level:acceso abierto
Palabra clave:RNA
Embryology
Anteroposterior axis
Symmetry breaking
Embryonic patterning
Gastruloids
Stem cell aggregates
Cell states
Embriologia
Àrees temàtiques de la UPC::Enginyeria biomèdica
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oai_identifier_str oai:upcommons.upc.edu:2117/423636
network_acronym_str ES
network_name_str España
repository_id_str
spelling Early autonomous patterning of the anteroposterior axis in gastruloidsAnlas, KerimGritti, NicolaNakaki, FumioSalamó Palau, LauraTlili, ShamOriola Santandreu, David|||0000-0002-8356-7832Arató, KrisztinaLim, Jia LeSharpe, JamesTrivedi, VikasRNAEmbryologyAnteroposterior axisSymmetry breakingEmbryonic patterningGastruloidsStem cell aggregatesCell statesRNAEmbriologiaÀrees temàtiques de la UPC::Enginyeria biomèdicaMinimal in vitro systems composed of embryonic stem cells (ESCs) have been shown to recapitulate the establishment of the anteroposterior (AP) axis. In contrast to the native embryo, ESC aggregates – such as gastruloids – can break symmetry, which is demarcated by polarization of the mesodermal marker T, autonomously without any localized external cues. However, associated earliest patterning events, such as the spatial restriction of cell fates and concomitant transcriptional changes, remain poorly understood. Here, we dissect the dynamics of AP axis establishment in mouse gastruloids, particularly before external Wnt stimulation. Through single-cell RNA sequencing, we identify key cell state transitions and the molecular signatures of T+ and T- populations underpinning AP polarization. We also show that this process is robust to modifications of aggregate size. Finally, transcriptomic comparison with the mouse embryo indicates that gastruloids develop similar mesendodermal cell types, despite initial differences in their primed pluripotent populations, which adopt a more mesenchymal state in lieu of an epiblast-like transcriptome. Hence, our findings suggest the possibility of alternate ESC states in vivo and in vitro that can converge onto similar cell fates.Peer Reviewed20242024-11-1520252025-02-10journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/2117/423636https://dx.doi.org/10.1242/dev.202171reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)InglésengAgencia Estatal de Investigación http://doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-128269NA-I00 BIOFISICA DE LA FORMACION DEL EJE ANTEROPOSTERIOR EN ORGANOIDES EMBRIONARIOS 3Dopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/4236362026-05-27T15:37:01Z
dc.title.none.fl_str_mv Early autonomous patterning of the anteroposterior axis in gastruloids
title Early autonomous patterning of the anteroposterior axis in gastruloids
spellingShingle Early autonomous patterning of the anteroposterior axis in gastruloids
Anlas, Kerim
RNA
Embryology
Anteroposterior axis
Symmetry breaking
Embryonic patterning
Gastruloids
Stem cell aggregates
Cell states
RNA
Embriologia
Àrees temàtiques de la UPC::Enginyeria biomèdica
title_short Early autonomous patterning of the anteroposterior axis in gastruloids
title_full Early autonomous patterning of the anteroposterior axis in gastruloids
title_fullStr Early autonomous patterning of the anteroposterior axis in gastruloids
title_full_unstemmed Early autonomous patterning of the anteroposterior axis in gastruloids
title_sort Early autonomous patterning of the anteroposterior axis in gastruloids
dc.creator.none.fl_str_mv Anlas, Kerim
Gritti, Nicola
Nakaki, Fumio
Salamó Palau, Laura
Tlili, Sham
Oriola Santandreu, David|||0000-0002-8356-7832
Arató, Krisztina
Lim, Jia Le
Sharpe, James
Trivedi, Vikas
author Anlas, Kerim
author_facet Anlas, Kerim
Gritti, Nicola
Nakaki, Fumio
Salamó Palau, Laura
Tlili, Sham
Oriola Santandreu, David|||0000-0002-8356-7832
Arató, Krisztina
Lim, Jia Le
Sharpe, James
Trivedi, Vikas
author_role author
author2 Gritti, Nicola
Nakaki, Fumio
Salamó Palau, Laura
Tlili, Sham
Oriola Santandreu, David|||0000-0002-8356-7832
Arató, Krisztina
Lim, Jia Le
Sharpe, James
Trivedi, Vikas
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv RNA
Embryology
Anteroposterior axis
Symmetry breaking
Embryonic patterning
Gastruloids
Stem cell aggregates
Cell states
RNA
Embriologia
Àrees temàtiques de la UPC::Enginyeria biomèdica
topic RNA
Embryology
Anteroposterior axis
Symmetry breaking
Embryonic patterning
Gastruloids
Stem cell aggregates
Cell states
RNA
Embriologia
Àrees temàtiques de la UPC::Enginyeria biomèdica
description Minimal in vitro systems composed of embryonic stem cells (ESCs) have been shown to recapitulate the establishment of the anteroposterior (AP) axis. In contrast to the native embryo, ESC aggregates – such as gastruloids – can break symmetry, which is demarcated by polarization of the mesodermal marker T, autonomously without any localized external cues. However, associated earliest patterning events, such as the spatial restriction of cell fates and concomitant transcriptional changes, remain poorly understood. Here, we dissect the dynamics of AP axis establishment in mouse gastruloids, particularly before external Wnt stimulation. Through single-cell RNA sequencing, we identify key cell state transitions and the molecular signatures of T+ and T- populations underpinning AP polarization. We also show that this process is robust to modifications of aggregate size. Finally, transcriptomic comparison with the mouse embryo indicates that gastruloids develop similar mesendodermal cell types, despite initial differences in their primed pluripotent populations, which adopt a more mesenchymal state in lieu of an epiblast-like transcriptome. Hence, our findings suggest the possibility of alternate ESC states in vivo and in vitro that can converge onto similar cell fates.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-11-15
2025
2025-02-10
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/423636
https://dx.doi.org/10.1242/dev.202171
url https://hdl.handle.net/2117/423636
https://dx.doi.org/10.1242/dev.202171
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-128269NA-I00 BIOFISICA DE LA FORMACION DEL EJE ANTEROPOSTERIOR EN ORGANOIDES EMBRIONARIOS 3D
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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