Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation

Autores
Neiman, Gabriel; Scarafia, Maria Agustina; la Greca, Alejandro Damián; Santín Velazque, Natalia Lucía; Garate, Ximena; Waisman, Ariel; Möbbs, Alan Miqueas; Kasai-Brunswick, Tais Hanae; Mesquita, Fernanda; Martire Greco, Daiana; Moro, Lucía Natalia; Luzzani, Carlos Daniel; Bastos Carvalho, Adriana; Sevlever, Gustavo; Campos de Carvalho, Antonio; Guberman, Alejandra Sonia; Miriuka, Santiago Gabriel
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The stem cell niche has a strong influence in the differentiation potential of human pluripotent stem cells with integrins playing a major role in communicating cells with the extracellular environment. However, it is not well understood how interactions between integrins and the extracellular matrix are involved in cardiac stem cell differentiation. To evaluate this, we performed a profile of integrins expression in two stages of cardiac differentiation: mesodermal progenitors and cardiomyocytes. We found an active regulation of the expression of different integrins during cardiac differentiation. In particular, integrin α5 subunit showed an increased expression in mesodermal progenitors, and a significant downregulation in cardiomyocytes. To analyze the effect of α5 subunit, we modified its expression by using a CRISPRi technique. After its downregulation, a significant impairment in the process of epithelial-to-mesenchymal transition was seen. Early mesoderm development was significantly affected due to a downregulation of key genes such as T Brachyury and TBX6. Furthermore, we observed that repression of integrin α5 during early stages led to a reduction in cardiomyocyte differentiation and impaired contractility. In summary, our results showed the link between changes in cell identity with the regulation of integrin α5 expression through the alteration of early stages of mesoderm commitment.
Fil: Neiman, Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Scarafia, Maria Agustina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: la Greca, Alejandro Damián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Santín Velazque, Natalia Lucía. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garate, Ximena. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Waisman, Ariel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Möbbs, Alan Miqueas. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kasai-Brunswick, Tais Hanae. Universidade Federal do Rio de Janeiro; Brasil
Fil: Mesquita, Fernanda. Universidade Federal do Rio de Janeiro; Brasil
Fil: Martire Greco, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Moro, Lucía Natalia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Luzzani, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Bastos Carvalho, Adriana. Universidade Federal do Rio de Janeiro; Brasil
Fil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Campos de Carvalho, Antonio. Universidade Federal do Rio de Janeiro; Brasil
Fil: Guberman, Alejandra Sonia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
PLURIPOTENT STEM CELLS
INTEGRIN
CARDIAC DIFFERENTIATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/175405
Acceder
id CONICETDig_b18283354d164f6011da55e812e13516
oai_identifier_str oai:ri.conicet.gov.ar:11336/175405
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiationNeiman, GabrielScarafia, Maria Agustinala Greca, Alejandro DamiánSantín Velazque, Natalia LucíaGarate, XimenaWaisman, ArielMöbbs, Alan MiqueasKasai-Brunswick, Tais HanaeMesquita, FernandaMartire Greco, DaianaMoro, Lucía NataliaLuzzani, Carlos DanielBastos Carvalho, AdrianaSevlever, GustavoCampos de Carvalho, AntonioGuberman, Alejandra SoniaMiriuka, Santiago GabrielPLURIPOTENT STEM CELLSINTEGRINCARDIAC DIFFERENTIATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The stem cell niche has a strong influence in the differentiation potential of human pluripotent stem cells with integrins playing a major role in communicating cells with the extracellular environment. However, it is not well understood how interactions between integrins and the extracellular matrix are involved in cardiac stem cell differentiation. To evaluate this, we performed a profile of integrins expression in two stages of cardiac differentiation: mesodermal progenitors and cardiomyocytes. We found an active regulation of the expression of different integrins during cardiac differentiation. In particular, integrin α5 subunit showed an increased expression in mesodermal progenitors, and a significant downregulation in cardiomyocytes. To analyze the effect of α5 subunit, we modified its expression by using a CRISPRi technique. After its downregulation, a significant impairment in the process of epithelial-to-mesenchymal transition was seen. Early mesoderm development was significantly affected due to a downregulation of key genes such as T Brachyury and TBX6. Furthermore, we observed that repression of integrin α5 during early stages led to a reduction in cardiomyocyte differentiation and impaired contractility. In summary, our results showed the link between changes in cell identity with the regulation of integrin α5 expression through the alteration of early stages of mesoderm commitment.Fil: Neiman, Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scarafia, Maria Agustina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: la Greca, Alejandro Damián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Santín Velazque, Natalia Lucía. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garate, Ximena. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Waisman, Ariel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Möbbs, Alan Miqueas. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kasai-Brunswick, Tais Hanae. Universidade Federal do Rio de Janeiro; BrasilFil: Mesquita, Fernanda. Universidade Federal do Rio de Janeiro; BrasilFil: Martire Greco, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Moro, Lucía Natalia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luzzani, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bastos Carvalho, Adriana. Universidade Federal do Rio de Janeiro; BrasilFil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Campos de Carvalho, Antonio. Universidade Federal do Rio de Janeiro; BrasilFil: Guberman, Alejandra Sonia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaNature2019-12info: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/11336/175405Neiman, Gabriel; Scarafia, Maria Agustina; la Greca, Alejandro Damián; Santín Velazque, Natalia Lucía; Garate, Ximena; et al.; Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation; Nature; Scientific Reports; 9; 1; 12-2019; 1-102045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-019-54352-2info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-54352-2info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:32Zoai:ri.conicet.gov.ar:11336/175405instacron: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 10:08:32.758CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
title Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
spellingShingle Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
Neiman, Gabriel
PLURIPOTENT STEM CELLS
INTEGRIN
CARDIAC DIFFERENTIATION
title_short Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
title_full Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
title_fullStr Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
title_full_unstemmed Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
title_sort Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
dc.creator.none.fl_str_mv Neiman, Gabriel
Scarafia, Maria Agustina
la Greca, Alejandro Damián
Santín Velazque, Natalia Lucía
Garate, Ximena
Waisman, Ariel
Möbbs, Alan Miqueas
Kasai-Brunswick, Tais Hanae
Mesquita, Fernanda
Martire Greco, Daiana
Moro, Lucía Natalia
Luzzani, Carlos Daniel
Bastos Carvalho, Adriana
Sevlever, Gustavo
Campos de Carvalho, Antonio
Guberman, Alejandra Sonia
Miriuka, Santiago Gabriel
author Neiman, Gabriel
author_facet Neiman, Gabriel
Scarafia, Maria Agustina
la Greca, Alejandro Damián
Santín Velazque, Natalia Lucía
Garate, Ximena
Waisman, Ariel
Möbbs, Alan Miqueas
Kasai-Brunswick, Tais Hanae
Mesquita, Fernanda
Martire Greco, Daiana
Moro, Lucía Natalia
Luzzani, Carlos Daniel
Bastos Carvalho, Adriana
Sevlever, Gustavo
Campos de Carvalho, Antonio
Guberman, Alejandra Sonia
Miriuka, Santiago Gabriel
author_role author
author2 Scarafia, Maria Agustina
la Greca, Alejandro Damián
Santín Velazque, Natalia Lucía
Garate, Ximena
Waisman, Ariel
Möbbs, Alan Miqueas
Kasai-Brunswick, Tais Hanae
Mesquita, Fernanda
Martire Greco, Daiana
Moro, Lucía Natalia
Luzzani, Carlos Daniel
Bastos Carvalho, Adriana
Sevlever, Gustavo
Campos de Carvalho, Antonio
Guberman, Alejandra Sonia
Miriuka, Santiago Gabriel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PLURIPOTENT STEM CELLS
INTEGRIN
CARDIAC DIFFERENTIATION
topic PLURIPOTENT STEM CELLS
INTEGRIN
CARDIAC DIFFERENTIATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The stem cell niche has a strong influence in the differentiation potential of human pluripotent stem cells with integrins playing a major role in communicating cells with the extracellular environment. However, it is not well understood how interactions between integrins and the extracellular matrix are involved in cardiac stem cell differentiation. To evaluate this, we performed a profile of integrins expression in two stages of cardiac differentiation: mesodermal progenitors and cardiomyocytes. We found an active regulation of the expression of different integrins during cardiac differentiation. In particular, integrin α5 subunit showed an increased expression in mesodermal progenitors, and a significant downregulation in cardiomyocytes. To analyze the effect of α5 subunit, we modified its expression by using a CRISPRi technique. After its downregulation, a significant impairment in the process of epithelial-to-mesenchymal transition was seen. Early mesoderm development was significantly affected due to a downregulation of key genes such as T Brachyury and TBX6. Furthermore, we observed that repression of integrin α5 during early stages led to a reduction in cardiomyocyte differentiation and impaired contractility. In summary, our results showed the link between changes in cell identity with the regulation of integrin α5 expression through the alteration of early stages of mesoderm commitment.
Fil: Neiman, Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Scarafia, Maria Agustina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: la Greca, Alejandro Damián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Santín Velazque, Natalia Lucía. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garate, Ximena. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Waisman, Ariel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Möbbs, Alan Miqueas. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kasai-Brunswick, Tais Hanae. Universidade Federal do Rio de Janeiro; Brasil
Fil: Mesquita, Fernanda. Universidade Federal do Rio de Janeiro; Brasil
Fil: Martire Greco, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Moro, Lucía Natalia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Luzzani, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Bastos Carvalho, Adriana. Universidade Federal do Rio de Janeiro; Brasil
Fil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Campos de Carvalho, Antonio. Universidade Federal do Rio de Janeiro; Brasil
Fil: Guberman, Alejandra Sonia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The stem cell niche has a strong influence in the differentiation potential of human pluripotent stem cells with integrins playing a major role in communicating cells with the extracellular environment. However, it is not well understood how interactions between integrins and the extracellular matrix are involved in cardiac stem cell differentiation. To evaluate this, we performed a profile of integrins expression in two stages of cardiac differentiation: mesodermal progenitors and cardiomyocytes. We found an active regulation of the expression of different integrins during cardiac differentiation. In particular, integrin α5 subunit showed an increased expression in mesodermal progenitors, and a significant downregulation in cardiomyocytes. To analyze the effect of α5 subunit, we modified its expression by using a CRISPRi technique. After its downregulation, a significant impairment in the process of epithelial-to-mesenchymal transition was seen. Early mesoderm development was significantly affected due to a downregulation of key genes such as T Brachyury and TBX6. Furthermore, we observed that repression of integrin α5 during early stages led to a reduction in cardiomyocyte differentiation and impaired contractility. In summary, our results showed the link between changes in cell identity with the regulation of integrin α5 expression through the alteration of early stages of mesoderm commitment.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
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/11336/175405
Neiman, Gabriel; Scarafia, Maria Agustina; la Greca, Alejandro Damián; Santín Velazque, Natalia Lucía; Garate, Ximena; et al.; Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation; Nature; Scientific Reports; 9; 1; 12-2019; 1-10
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/175405
identifier_str_mv Neiman, Gabriel; Scarafia, Maria Agustina; la Greca, Alejandro Damián; Santín Velazque, Natalia Lucía; Garate, Ximena; et al.; Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation; Nature; Scientific Reports; 9; 1; 12-2019; 1-10
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-019-54352-2
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-54352-2
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
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 13.13397

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