Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions

Autores
Peregrina, Karina; Houston, Michele; Daroqui, Maria Cecilia; Dhima, Elena; Sellers, Rani S.; Augenlicht, Leonard H.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lgr5+ intestinal crypt base columnar cells function as stem cells whose progeny populate the villi, and Lgr5+ cells in which Apc is inactivated can give rise to tumors. Surprisingly, these Lgr5+ stem cell properties were abrogated by the lower dietary vitamin D and calcium in a semi-purified diet that promotes both genetically initiated and sporadic intestinal tumors. Inactivation of the vitamin D receptor in Lgr5+ cells established that compromise of Lgr5 stem cell function was a rapid, cell autonomous effect of signaling through the vitamin D receptor. The loss of Lgr5 stem cell function was associated with presence of Ki67 negative Lgr5+ cells at the crypt base. Therefore, vitamin D, a common nutrient and inducer of intestinal cell maturation, is an environmental factor that is a determinant of Lgr5+ stem cell functions in vivo. Since diets used in reports that establish and dissect mouse Lgr5+ stem cell activity likely provided vitamin D levels well above the range documented for human populations, the contribution of Lgr5+ cells to intestinal homeostasis and tumor formation in humans may be significantly more limited, and variable in the population, then suggested by published rodent studies.
Fil: Peregrina, Karina. Albert Einstein College of Medicine; Estados Unidos
Fil: Houston, Michele. Albert Einstein College of Medicine; Estados Unidos
Fil: Daroqui, Maria Cecilia. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dhima, Elena. Albert Einstein College of Medicine; Estados Unidos
Fil: Sellers, Rani S.. Albert Einstein College of Medicine; Estados Unidos
Fil: Augenlicht, Leonard H.. Albert Einstein College of Medicine; Estados Unidos
Materia
Vitamind
Lgr5
Stemcell
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:11336/37848
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/37848
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functionsPeregrina, KarinaHouston, MicheleDaroqui, Maria CeciliaDhima, ElenaSellers, Rani S.Augenlicht, Leonard H.VitamindLgr5Stemcellhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Lgr5+ intestinal crypt base columnar cells function as stem cells whose progeny populate the villi, and Lgr5+ cells in which Apc is inactivated can give rise to tumors. Surprisingly, these Lgr5+ stem cell properties were abrogated by the lower dietary vitamin D and calcium in a semi-purified diet that promotes both genetically initiated and sporadic intestinal tumors. Inactivation of the vitamin D receptor in Lgr5+ cells established that compromise of Lgr5 stem cell function was a rapid, cell autonomous effect of signaling through the vitamin D receptor. The loss of Lgr5 stem cell function was associated with presence of Ki67 negative Lgr5+ cells at the crypt base. Therefore, vitamin D, a common nutrient and inducer of intestinal cell maturation, is an environmental factor that is a determinant of Lgr5+ stem cell functions in vivo. Since diets used in reports that establish and dissect mouse Lgr5+ stem cell activity likely provided vitamin D levels well above the range documented for human populations, the contribution of Lgr5+ cells to intestinal homeostasis and tumor formation in humans may be significantly more limited, and variable in the population, then suggested by published rodent studies.Fil: Peregrina, Karina. Albert Einstein College of Medicine; Estados UnidosFil: Houston, Michele. Albert Einstein College of Medicine; Estados UnidosFil: Daroqui, Maria Cecilia. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dhima, Elena. Albert Einstein College of Medicine; Estados UnidosFil: Sellers, Rani S.. Albert Einstein College of Medicine; Estados UnidosFil: Augenlicht, Leonard H.. Albert Einstein College of Medicine; Estados UnidosOxford University Press2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/37848Peregrina, Karina; Houston, Michele; Daroqui, Maria Cecilia; Dhima, Elena; Sellers, Rani S.; et al.; Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions; Oxford University Press; Carcinogenesis; 36; 1; 1-2015; 25-311460-2180CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/carcin/bgu221info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/carcin/article/36/1/25/376913info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:35:31Zoai:ri.conicet.gov.ar:11336/37848instacron: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 14:35:31.533CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions
title Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions
spellingShingle Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions
Peregrina, Karina
Vitamind
Lgr5
Stemcell
title_short Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions
title_full Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions
title_fullStr Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions
title_full_unstemmed Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions
title_sort Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions
dc.creator.none.fl_str_mv Peregrina, Karina
Houston, Michele
Daroqui, Maria Cecilia
Dhima, Elena
Sellers, Rani S.
Augenlicht, Leonard H.
author Peregrina, Karina
author_facet Peregrina, Karina
Houston, Michele
Daroqui, Maria Cecilia
Dhima, Elena
Sellers, Rani S.
Augenlicht, Leonard H.
author_role author
author2 Houston, Michele
Daroqui, Maria Cecilia
Dhima, Elena
Sellers, Rani S.
Augenlicht, Leonard H.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Vitamind
Lgr5
Stemcell
topic Vitamind
Lgr5
Stemcell
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Lgr5+ intestinal crypt base columnar cells function as stem cells whose progeny populate the villi, and Lgr5+ cells in which Apc is inactivated can give rise to tumors. Surprisingly, these Lgr5+ stem cell properties were abrogated by the lower dietary vitamin D and calcium in a semi-purified diet that promotes both genetically initiated and sporadic intestinal tumors. Inactivation of the vitamin D receptor in Lgr5+ cells established that compromise of Lgr5 stem cell function was a rapid, cell autonomous effect of signaling through the vitamin D receptor. The loss of Lgr5 stem cell function was associated with presence of Ki67 negative Lgr5+ cells at the crypt base. Therefore, vitamin D, a common nutrient and inducer of intestinal cell maturation, is an environmental factor that is a determinant of Lgr5+ stem cell functions in vivo. Since diets used in reports that establish and dissect mouse Lgr5+ stem cell activity likely provided vitamin D levels well above the range documented for human populations, the contribution of Lgr5+ cells to intestinal homeostasis and tumor formation in humans may be significantly more limited, and variable in the population, then suggested by published rodent studies.
Fil: Peregrina, Karina. Albert Einstein College of Medicine; Estados Unidos
Fil: Houston, Michele. Albert Einstein College of Medicine; Estados Unidos
Fil: Daroqui, Maria Cecilia. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dhima, Elena. Albert Einstein College of Medicine; Estados Unidos
Fil: Sellers, Rani S.. Albert Einstein College of Medicine; Estados Unidos
Fil: Augenlicht, Leonard H.. Albert Einstein College of Medicine; Estados Unidos
description Lgr5+ intestinal crypt base columnar cells function as stem cells whose progeny populate the villi, and Lgr5+ cells in which Apc is inactivated can give rise to tumors. Surprisingly, these Lgr5+ stem cell properties were abrogated by the lower dietary vitamin D and calcium in a semi-purified diet that promotes both genetically initiated and sporadic intestinal tumors. Inactivation of the vitamin D receptor in Lgr5+ cells established that compromise of Lgr5 stem cell function was a rapid, cell autonomous effect of signaling through the vitamin D receptor. The loss of Lgr5 stem cell function was associated with presence of Ki67 negative Lgr5+ cells at the crypt base. Therefore, vitamin D, a common nutrient and inducer of intestinal cell maturation, is an environmental factor that is a determinant of Lgr5+ stem cell functions in vivo. Since diets used in reports that establish and dissect mouse Lgr5+ stem cell activity likely provided vitamin D levels well above the range documented for human populations, the contribution of Lgr5+ cells to intestinal homeostasis and tumor formation in humans may be significantly more limited, and variable in the population, then suggested by published rodent studies.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
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/11336/37848
Peregrina, Karina; Houston, Michele; Daroqui, Maria Cecilia; Dhima, Elena; Sellers, Rani S.; et al.; Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions; Oxford University Press; Carcinogenesis; 36; 1; 1-2015; 25-31
1460-2180
CONICET Digital
CONICET
url http://hdl.handle.net/11336/37848
identifier_str_mv Peregrina, Karina; Houston, Michele; Daroqui, Maria Cecilia; Dhima, Elena; Sellers, Rani S.; et al.; Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions; Oxford University Press; Carcinogenesis; 36; 1; 1-2015; 25-31
1460-2180
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/carcin/bgu221
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/carcin/article/36/1/25/376913
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
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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
_version_ 1846082815226019840
score 13.22299

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