Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives

Autores
Mendez Maldonado, Karla; Vega López, Guillermo Alfredo; Caballero Chacón, Sara; Aybar, Manuel Javier; Velasco, Ivan
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The neural crest (NC) comprises an ectodermal multipotent cell population that produces peripheral neurons, cartilage and smooth muscle cells, among other phenotypes. The participation of Hes1 and Msx1 when expressed in mouse embryonic stem cells (mESCs) undergoing NC differentiation is unexplored. In this work, we generated stable mESCs transfected with constructs encoding chimeric proteins in which the ligand binding domain of glucocorticoid receptor (GR), which is translocated to the nucleus by dexamethasone addition, is fused to either Hes1 (HGR) or Msx1 (MGR), as well as double-transgenic cells (HGR+MGR). These lines continued to express pluripotency markers. Upon NC differentiation, all lines exhibited significantly decreased Sox2 expression and upregulated Sox9, Snai1 and Msx1 expression, indicating NC commitment. In parallel experiments, dexamethasone was added to induce nuclear translocation of the chimeric proteins at early stages, and we found that Collagen IIa transcripts were increased in MGR cells, whereas coactivation of HGR+MGR caused a significant increase in Smooth muscle actin (alpha-Sma) transcripts. Immunostaining showed that activation in HGR+MGR cells induced higher proportions of BETA-TUBULIN III+ and alpha-SMA+ cells. These findings indicate that nuclear translocation of MSX1 might be used to produce chondrocytes at higher efficiencies, but simultaneous activation of HES1 and MSX1 increases the generation of smooth muscle and neuronal cells.
Fil: Mendez Maldonado, Karla. Universidad Nacional Autónoma de México; México
Fil: Vega López, Guillermo Alfredo. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina
Fil: Caballero Chacón, Sara. Universidad Nacional Autónoma de México; México
Fil: Aybar, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina
Fil: Velasco, Ivan. Universidad Nacional Autónoma de México; México
Materia
STEM CELLS
CELL DIFFERENTIATION
TRANSCRIPTION FACTORS
NEURAL CREST
CELL LINEAGES
SMOOTH MUSCLE CELLS INDUCTION
CHONDROCYTES INDUCTION
EMBRYONIC STEM CELLS
CELL SIGNALING
β-TUBULIN III
STROMAL-DERIVED INDUCING ACTIVITY
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:11336/101934
Acceder
id CONICETDig_9fbf647e60e83bb0e0af625e199797e0
oai_identifier_str oai:ri.conicet.gov.ar:11336/101934
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivativesMendez Maldonado, KarlaVega López, Guillermo AlfredoCaballero Chacón, SaraAybar, Manuel JavierVelasco, IvanSTEM CELLSCELL DIFFERENTIATIONTRANSCRIPTION FACTORSNEURAL CRESTCELL LINEAGESSMOOTH MUSCLE CELLS INDUCTIONCHONDROCYTES INDUCTIONEMBRYONIC STEM CELLSCELL SIGNALINGβ-TUBULIN IIISTROMAL-DERIVED INDUCING ACTIVITYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The neural crest (NC) comprises an ectodermal multipotent cell population that produces peripheral neurons, cartilage and smooth muscle cells, among other phenotypes. The participation of Hes1 and Msx1 when expressed in mouse embryonic stem cells (mESCs) undergoing NC differentiation is unexplored. In this work, we generated stable mESCs transfected with constructs encoding chimeric proteins in which the ligand binding domain of glucocorticoid receptor (GR), which is translocated to the nucleus by dexamethasone addition, is fused to either Hes1 (HGR) or Msx1 (MGR), as well as double-transgenic cells (HGR+MGR). These lines continued to express pluripotency markers. Upon NC differentiation, all lines exhibited significantly decreased Sox2 expression and upregulated Sox9, Snai1 and Msx1 expression, indicating NC commitment. In parallel experiments, dexamethasone was added to induce nuclear translocation of the chimeric proteins at early stages, and we found that Collagen IIa transcripts were increased in MGR cells, whereas coactivation of HGR+MGR caused a significant increase in Smooth muscle actin (alpha-Sma) transcripts. Immunostaining showed that activation in HGR+MGR cells induced higher proportions of BETA-TUBULIN III+ and alpha-SMA+ cells. These findings indicate that nuclear translocation of MSX1 might be used to produce chondrocytes at higher efficiencies, but simultaneous activation of HES1 and MSX1 increases the generation of smooth muscle and neuronal cells.Fil: Mendez Maldonado, Karla. Universidad Nacional Autónoma de México; MéxicoFil: Vega López, Guillermo Alfredo. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Caballero Chacón, Sara. Universidad Nacional Autónoma de México; MéxicoFil: Aybar, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Velasco, Ivan. Universidad Nacional Autónoma de México; MéxicoMDPI2018-12info: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/11336/101934Mendez Maldonado, Karla; Vega López, Guillermo Alfredo; Caballero Chacón, Sara; Aybar, Manuel Javier; Velasco, Ivan; Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives; MDPI; International Journal of Molecular Sciences; 19; 12; 12-2018; 1-231422-00671422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/19/12/4025info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms19124025info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:36Zoai:ri.conicet.gov.ar:11336/101934instacron: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:34982025-09-29 10:15:36.383CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives
title Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives
spellingShingle Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives
Mendez Maldonado, Karla
STEM CELLS
CELL DIFFERENTIATION
TRANSCRIPTION FACTORS
NEURAL CREST
CELL LINEAGES
SMOOTH MUSCLE CELLS INDUCTION
CHONDROCYTES INDUCTION
EMBRYONIC STEM CELLS
CELL SIGNALING
β-TUBULIN III
STROMAL-DERIVED INDUCING ACTIVITY
title_short Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives
title_full Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives
title_fullStr Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives
title_full_unstemmed Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives
title_sort Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives
dc.creator.none.fl_str_mv Mendez Maldonado, Karla
Vega López, Guillermo Alfredo
Caballero Chacón, Sara
Aybar, Manuel Javier
Velasco, Ivan
author Mendez Maldonado, Karla
author_facet Mendez Maldonado, Karla
Vega López, Guillermo Alfredo
Caballero Chacón, Sara
Aybar, Manuel Javier
Velasco, Ivan
author_role author
author2 Vega López, Guillermo Alfredo
Caballero Chacón, Sara
Aybar, Manuel Javier
Velasco, Ivan
author2_role author
author
author
author
dc.subject.none.fl_str_mv STEM CELLS
CELL DIFFERENTIATION
TRANSCRIPTION FACTORS
NEURAL CREST
CELL LINEAGES
SMOOTH MUSCLE CELLS INDUCTION
CHONDROCYTES INDUCTION
EMBRYONIC STEM CELLS
CELL SIGNALING
β-TUBULIN III
STROMAL-DERIVED INDUCING ACTIVITY
topic STEM CELLS
CELL DIFFERENTIATION
TRANSCRIPTION FACTORS
NEURAL CREST
CELL LINEAGES
SMOOTH MUSCLE CELLS INDUCTION
CHONDROCYTES INDUCTION
EMBRYONIC STEM CELLS
CELL SIGNALING
β-TUBULIN III
STROMAL-DERIVED INDUCING ACTIVITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The neural crest (NC) comprises an ectodermal multipotent cell population that produces peripheral neurons, cartilage and smooth muscle cells, among other phenotypes. The participation of Hes1 and Msx1 when expressed in mouse embryonic stem cells (mESCs) undergoing NC differentiation is unexplored. In this work, we generated stable mESCs transfected with constructs encoding chimeric proteins in which the ligand binding domain of glucocorticoid receptor (GR), which is translocated to the nucleus by dexamethasone addition, is fused to either Hes1 (HGR) or Msx1 (MGR), as well as double-transgenic cells (HGR+MGR). These lines continued to express pluripotency markers. Upon NC differentiation, all lines exhibited significantly decreased Sox2 expression and upregulated Sox9, Snai1 and Msx1 expression, indicating NC commitment. In parallel experiments, dexamethasone was added to induce nuclear translocation of the chimeric proteins at early stages, and we found that Collagen IIa transcripts were increased in MGR cells, whereas coactivation of HGR+MGR caused a significant increase in Smooth muscle actin (alpha-Sma) transcripts. Immunostaining showed that activation in HGR+MGR cells induced higher proportions of BETA-TUBULIN III+ and alpha-SMA+ cells. These findings indicate that nuclear translocation of MSX1 might be used to produce chondrocytes at higher efficiencies, but simultaneous activation of HES1 and MSX1 increases the generation of smooth muscle and neuronal cells.
Fil: Mendez Maldonado, Karla. Universidad Nacional Autónoma de México; México
Fil: Vega López, Guillermo Alfredo. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina
Fil: Caballero Chacón, Sara. Universidad Nacional Autónoma de México; México
Fil: Aybar, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina
Fil: Velasco, Ivan. Universidad Nacional Autónoma de México; México
description The neural crest (NC) comprises an ectodermal multipotent cell population that produces peripheral neurons, cartilage and smooth muscle cells, among other phenotypes. The participation of Hes1 and Msx1 when expressed in mouse embryonic stem cells (mESCs) undergoing NC differentiation is unexplored. In this work, we generated stable mESCs transfected with constructs encoding chimeric proteins in which the ligand binding domain of glucocorticoid receptor (GR), which is translocated to the nucleus by dexamethasone addition, is fused to either Hes1 (HGR) or Msx1 (MGR), as well as double-transgenic cells (HGR+MGR). These lines continued to express pluripotency markers. Upon NC differentiation, all lines exhibited significantly decreased Sox2 expression and upregulated Sox9, Snai1 and Msx1 expression, indicating NC commitment. In parallel experiments, dexamethasone was added to induce nuclear translocation of the chimeric proteins at early stages, and we found that Collagen IIa transcripts were increased in MGR cells, whereas coactivation of HGR+MGR caused a significant increase in Smooth muscle actin (alpha-Sma) transcripts. Immunostaining showed that activation in HGR+MGR cells induced higher proportions of BETA-TUBULIN III+ and alpha-SMA+ cells. These findings indicate that nuclear translocation of MSX1 might be used to produce chondrocytes at higher efficiencies, but simultaneous activation of HES1 and MSX1 increases the generation of smooth muscle and neuronal cells.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/101934
Mendez Maldonado, Karla; Vega López, Guillermo Alfredo; Caballero Chacón, Sara; Aybar, Manuel Javier; Velasco, Ivan; Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives; MDPI; International Journal of Molecular Sciences; 19; 12; 12-2018; 1-23
1422-0067
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/101934
identifier_str_mv Mendez Maldonado, Karla; Vega López, Guillermo Alfredo; Caballero Chacón, Sara; Aybar, Manuel Javier; Velasco, Ivan; Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives; MDPI; International Journal of Molecular Sciences; 19; 12; 12-2018; 1-23
1422-0067
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.mdpi.com/1422-0067/19/12/4025
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms19124025
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
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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score 13.070432

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