The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase

Autores
Oses Oliveto, Camila Maite; Francia, Marcos Gabriel; Verneri, Paula; Vazquez Echegaray, Camila; Guberman, Alejandra Sonia; Levi, Valeria
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
DNA replication in stem cells is a major challenge for pluripotency preservation and cell fate decisions. This process involves massive changes in the chromatin architecture and the reorganization of many transcription-related molecules in different spatial and temporal scales. Pluripotency is controlled by the master transcription factors (TFs) OCT4, SOX2 and NANOG that partition into condensates in the nucleus of embryonic stem cells. These condensates are proposed to play relevant roles in the regulation of gene expression and the maintenance of pluripotency. Here, we asked whether the dynamical distribution of the pluripotency TFs changes during the cell cycle, particularly during DNA replication. Since the S phase is considered to be a window of opportunity for cell fate decisions, we explored if differentiation cues in G1 phase trigger changes in the distribution of these TFs during the subsequent S phase. Our results show a spatial redistribution of TFs condensates during DNA replication which was not directly related to chromatin compaction. Additionally, fluorescence fluctuation spectroscopy revealed TF-specific, subtle changes in the landscape of TF-chromatin interactions, consistent with their particularities as key players of the pluripotency network. Moreover, we found that differentiation stimuli in the preceding G1 phase triggered a relatively fast and massive reorganization of pluripotency TFs in early-S phase. Particularly, OCT4 and SOX2 condensates dissolved whereas the lifetimes of TF-chromatin interactions increased suggesting that the reorganization of condensates is accompanied with a change in the landscape of TF-chromatin interactions. Notably, NANOG showed impaired interactions with chromatin in stimulated early-S cells in line with its role as naïve pluripotency TF. Together, these findings provide new insights into the regulation of the core pluripotency TFs during DNA replication of embryonic stem cells and highlight their different roles at early differentiation stages.
Fil: Oses Oliveto, Camila Maite. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Francia, Marcos Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Verneri, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Vazquez Echegaray, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Guberman, Alejandra Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Levi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
CELL CYCLE
CONDENSATES
DIFFERENTIATION
DNA REPLICATION
EMBRYONIC STEM CELLS
PLURIPOTENCY TRANSCRIPTION FACTORS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/228530
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/228530
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phaseOses Oliveto, Camila MaiteFrancia, Marcos GabrielVerneri, PaulaVazquez Echegaray, CamilaGuberman, Alejandra SoniaLevi, ValeriaCELL CYCLECONDENSATESDIFFERENTIATIONDNA REPLICATIONEMBRYONIC STEM CELLSPLURIPOTENCY TRANSCRIPTION FACTORShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1DNA replication in stem cells is a major challenge for pluripotency preservation and cell fate decisions. This process involves massive changes in the chromatin architecture and the reorganization of many transcription-related molecules in different spatial and temporal scales. Pluripotency is controlled by the master transcription factors (TFs) OCT4, SOX2 and NANOG that partition into condensates in the nucleus of embryonic stem cells. These condensates are proposed to play relevant roles in the regulation of gene expression and the maintenance of pluripotency. Here, we asked whether the dynamical distribution of the pluripotency TFs changes during the cell cycle, particularly during DNA replication. Since the S phase is considered to be a window of opportunity for cell fate decisions, we explored if differentiation cues in G1 phase trigger changes in the distribution of these TFs during the subsequent S phase. Our results show a spatial redistribution of TFs condensates during DNA replication which was not directly related to chromatin compaction. Additionally, fluorescence fluctuation spectroscopy revealed TF-specific, subtle changes in the landscape of TF-chromatin interactions, consistent with their particularities as key players of the pluripotency network. Moreover, we found that differentiation stimuli in the preceding G1 phase triggered a relatively fast and massive reorganization of pluripotency TFs in early-S phase. Particularly, OCT4 and SOX2 condensates dissolved whereas the lifetimes of TF-chromatin interactions increased suggesting that the reorganization of condensates is accompanied with a change in the landscape of TF-chromatin interactions. Notably, NANOG showed impaired interactions with chromatin in stimulated early-S cells in line with its role as naïve pluripotency TF. Together, these findings provide new insights into the regulation of the core pluripotency TFs during DNA replication of embryonic stem cells and highlight their different roles at early differentiation stages.Fil: Oses Oliveto, Camila Maite. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Francia, Marcos Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Verneri, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Vazquez Echegaray, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Guberman, Alejandra Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Levi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFrontiers Media2023-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228530Oses Oliveto, Camila Maite; Francia, Marcos Gabriel; Verneri, Paula; Vazquez Echegaray, Camila; Guberman, Alejandra Sonia; et al.; The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase; Frontiers Media; Frontiers in Cell and Developmental Biology; 11; 5-2023; 1-162296-634XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fcell.2023.1125015/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fcell.2023.1125015info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:10Zoai:ri.conicet.gov.ar:11336/228530instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:07:10.431CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase
title The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase
spellingShingle The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase
Oses Oliveto, Camila Maite
CELL CYCLE
CONDENSATES
DIFFERENTIATION
DNA REPLICATION
EMBRYONIC STEM CELLS
PLURIPOTENCY TRANSCRIPTION FACTORS
title_short The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase
title_full The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase
title_fullStr The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase
title_full_unstemmed The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase
title_sort The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase
dc.creator.none.fl_str_mv Oses Oliveto, Camila Maite
Francia, Marcos Gabriel
Verneri, Paula
Vazquez Echegaray, Camila
Guberman, Alejandra Sonia
Levi, Valeria
author Oses Oliveto, Camila Maite
author_facet Oses Oliveto, Camila Maite
Francia, Marcos Gabriel
Verneri, Paula
Vazquez Echegaray, Camila
Guberman, Alejandra Sonia
Levi, Valeria
author_role author
author2 Francia, Marcos Gabriel
Verneri, Paula
Vazquez Echegaray, Camila
Guberman, Alejandra Sonia
Levi, Valeria
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CELL CYCLE
CONDENSATES
DIFFERENTIATION
DNA REPLICATION
EMBRYONIC STEM CELLS
PLURIPOTENCY TRANSCRIPTION FACTORS
topic CELL CYCLE
CONDENSATES
DIFFERENTIATION
DNA REPLICATION
EMBRYONIC STEM CELLS
PLURIPOTENCY TRANSCRIPTION FACTORS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv DNA replication in stem cells is a major challenge for pluripotency preservation and cell fate decisions. This process involves massive changes in the chromatin architecture and the reorganization of many transcription-related molecules in different spatial and temporal scales. Pluripotency is controlled by the master transcription factors (TFs) OCT4, SOX2 and NANOG that partition into condensates in the nucleus of embryonic stem cells. These condensates are proposed to play relevant roles in the regulation of gene expression and the maintenance of pluripotency. Here, we asked whether the dynamical distribution of the pluripotency TFs changes during the cell cycle, particularly during DNA replication. Since the S phase is considered to be a window of opportunity for cell fate decisions, we explored if differentiation cues in G1 phase trigger changes in the distribution of these TFs during the subsequent S phase. Our results show a spatial redistribution of TFs condensates during DNA replication which was not directly related to chromatin compaction. Additionally, fluorescence fluctuation spectroscopy revealed TF-specific, subtle changes in the landscape of TF-chromatin interactions, consistent with their particularities as key players of the pluripotency network. Moreover, we found that differentiation stimuli in the preceding G1 phase triggered a relatively fast and massive reorganization of pluripotency TFs in early-S phase. Particularly, OCT4 and SOX2 condensates dissolved whereas the lifetimes of TF-chromatin interactions increased suggesting that the reorganization of condensates is accompanied with a change in the landscape of TF-chromatin interactions. Notably, NANOG showed impaired interactions with chromatin in stimulated early-S cells in line with its role as naïve pluripotency TF. Together, these findings provide new insights into the regulation of the core pluripotency TFs during DNA replication of embryonic stem cells and highlight their different roles at early differentiation stages.
Fil: Oses Oliveto, Camila Maite. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Francia, Marcos Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Verneri, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Vazquez Echegaray, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Guberman, Alejandra Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Levi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description DNA replication in stem cells is a major challenge for pluripotency preservation and cell fate decisions. This process involves massive changes in the chromatin architecture and the reorganization of many transcription-related molecules in different spatial and temporal scales. Pluripotency is controlled by the master transcription factors (TFs) OCT4, SOX2 and NANOG that partition into condensates in the nucleus of embryonic stem cells. These condensates are proposed to play relevant roles in the regulation of gene expression and the maintenance of pluripotency. Here, we asked whether the dynamical distribution of the pluripotency TFs changes during the cell cycle, particularly during DNA replication. Since the S phase is considered to be a window of opportunity for cell fate decisions, we explored if differentiation cues in G1 phase trigger changes in the distribution of these TFs during the subsequent S phase. Our results show a spatial redistribution of TFs condensates during DNA replication which was not directly related to chromatin compaction. Additionally, fluorescence fluctuation spectroscopy revealed TF-specific, subtle changes in the landscape of TF-chromatin interactions, consistent with their particularities as key players of the pluripotency network. Moreover, we found that differentiation stimuli in the preceding G1 phase triggered a relatively fast and massive reorganization of pluripotency TFs in early-S phase. Particularly, OCT4 and SOX2 condensates dissolved whereas the lifetimes of TF-chromatin interactions increased suggesting that the reorganization of condensates is accompanied with a change in the landscape of TF-chromatin interactions. Notably, NANOG showed impaired interactions with chromatin in stimulated early-S cells in line with its role as naïve pluripotency TF. Together, these findings provide new insights into the regulation of the core pluripotency TFs during DNA replication of embryonic stem cells and highlight their different roles at early differentiation stages.
publishDate 2023
dc.date.none.fl_str_mv 2023-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/228530
Oses Oliveto, Camila Maite; Francia, Marcos Gabriel; Verneri, Paula; Vazquez Echegaray, Camila; Guberman, Alejandra Sonia; et al.; The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase; Frontiers Media; Frontiers in Cell and Developmental Biology; 11; 5-2023; 1-16
2296-634X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/228530
identifier_str_mv Oses Oliveto, Camila Maite; Francia, Marcos Gabriel; Verneri, Paula; Vazquez Echegaray, Camila; Guberman, Alejandra Sonia; et al.; The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase; Frontiers Media; Frontiers in Cell and Developmental Biology; 11; 5-2023; 1-16
2296-634X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fcell.2023.1125015/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fcell.2023.1125015
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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