PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells

Autores
Pérez Millán, María Inés; Brinkmeier, Michelle; Mortensen, Amanda H; Camper, Sally
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines. We determined that PROP1 is essential for stimulating stem cells to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to genes expressed in epithelial cells like Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2. Zeb2 activation appears to be a key step in the EMT process. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.
Fil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Brinkmeier, Michelle. University of Michigan; Estados Unidos
Fil: Mortensen, Amanda H. University of Michigan; Estados Unidos
Fil: Camper, Sally. University of Michigan; Estados Unidos
Materia
PROP1
STEM CELLS
EMT
HIPOPITUITARISM
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:11336/48575
Acceder
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network_name_str CONICET Digital (CONICET)
spelling PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cellsPérez Millán, María InésBrinkmeier, MichelleMortensen, Amanda HCamper, SallyPROP1STEM CELLSEMTHIPOPITUITARISMhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines. We determined that PROP1 is essential for stimulating stem cells to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to genes expressed in epithelial cells like Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2. Zeb2 activation appears to be a key step in the EMT process. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.Fil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Brinkmeier, Michelle. University of Michigan; Estados UnidosFil: Mortensen, Amanda H. University of Michigan; Estados UnidosFil: Camper, Sally. University of Michigan; Estados UnidoseLife Sciences Publications Ltd2016-06info: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/11336/48575Pérez Millán, María Inés; Brinkmeier, Michelle; Mortensen, Amanda H; Camper, Sally; PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells; eLife Sciences Publications Ltd; eLIFE; 5; 6-20162050-084XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.14470info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940164/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:16:50Zoai:ri.conicet.gov.ar:11336/48575instacron: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:34982025-10-15 15:16:51.218CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
title PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
spellingShingle PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
Pérez Millán, María Inés
PROP1
STEM CELLS
EMT
HIPOPITUITARISM
title_short PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
title_full PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
title_fullStr PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
title_full_unstemmed PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
title_sort PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells
dc.creator.none.fl_str_mv Pérez Millán, María Inés
Brinkmeier, Michelle
Mortensen, Amanda H
Camper, Sally
author Pérez Millán, María Inés
author_facet Pérez Millán, María Inés
Brinkmeier, Michelle
Mortensen, Amanda H
Camper, Sally
author_role author
author2 Brinkmeier, Michelle
Mortensen, Amanda H
Camper, Sally
author2_role author
author
author
dc.subject.none.fl_str_mv PROP1
STEM CELLS
EMT
HIPOPITUITARISM
topic PROP1
STEM CELLS
EMT
HIPOPITUITARISM
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines. We determined that PROP1 is essential for stimulating stem cells to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to genes expressed in epithelial cells like Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2. Zeb2 activation appears to be a key step in the EMT process. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.
Fil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Brinkmeier, Michelle. University of Michigan; Estados Unidos
Fil: Mortensen, Amanda H. University of Michigan; Estados Unidos
Fil: Camper, Sally. University of Michigan; Estados Unidos
description Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines. We determined that PROP1 is essential for stimulating stem cells to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to genes expressed in epithelial cells like Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2. Zeb2 activation appears to be a key step in the EMT process. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.
publishDate 2016
dc.date.none.fl_str_mv 2016-06
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/11336/48575
Pérez Millán, María Inés; Brinkmeier, Michelle; Mortensen, Amanda H; Camper, Sally; PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells; eLife Sciences Publications Ltd; eLIFE; 5; 6-2016
2050-084X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48575
identifier_str_mv Pérez Millán, María Inés; Brinkmeier, Michelle; Mortensen, Amanda H; Camper, Sally; PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells; eLife Sciences Publications Ltd; eLIFE; 5; 6-2016
2050-084X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.14470
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940164/
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 eLife Sciences Publications Ltd
publisher.none.fl_str_mv eLife Sciences Publications Ltd
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 12.891075

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