Mostrar el registro sencillo del ítem

dc.contributor.authorSantos, Catarina P
dc.contributor.authorLapi, Eleonora
dc.contributor.authorMartínez de Villarreal, Jaime
dc.contributor.authorÁlvaro-Espinosa, Laura
dc.contributor.authorFernández-Barral, Asunción
dc.contributor.authorBarbáchano, Antonio
dc.contributor.authorDominguez, Orlando 
dc.contributor.authorLaughney, Ashley M
dc.contributor.authorMegias Vazquez, Diego 
dc.contributor.authorMuñoz, Alberto
dc.contributor.authorReal Arribas, Francisco 
dc.date.accessioned2020-03-24T19:12:44Z
dc.date.available2020-03-24T19:12:44Z
dc.date.issued2019-09-27
dc.identifier.citationNat Commun. 2019;10(1):4407.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9319
dc.description.abstractUnderstanding urothelial stem cell biology and differentiation has been limited by the lack of methods for their unlimited propagation. Here, we establish mouse urothelial organoids that can be maintained uninterruptedly for >1 year. Organoid growth is dependent on EGF and Wnt activators. High CD49f/ITGA6 expression features a subpopulation of organoid-forming cells expressing basal markers. Upon differentiation, multilayered organoids undergo reduced proliferation, decreased cell layer number, urothelial program activation, and acquisition of barrier function. Pharmacological modulation of PPARγ and EGFR promotes differentiation. RNA sequencing highlighted genesets enriched in proliferative organoids (i.e. ribosome) and transcriptional networks involved in differentiation, including expression of Wnt ligands and Notch components. Single-cell RNA sequencing (scRNA-Seq) analysis of the organoids revealed five clusters with distinct gene expression profiles. Together, with the use of γ-secretase inhibitors and scRNA-Seq, confirms that Notch signaling is required for differentiation. Urothelial organoids provide a powerful tool to study cell regeneration and differentiation.es_ES
dc.description.sponsorshipWe thank the members of the Epithelial Carcinogenesis Group and the CNIO Bioinformatics Unit for valuable discussions; N. del Pozo, Y. Gonzalo, and R. Serrano for help with animal experimentation; E. Carrillo-de-Santa-Pau and O. Grana for help with bioinformatics analyses; E. Osinaga for help with lectin assays; A. Garcia-Espana for providing antibodies; A. Bigas, D. Chondronasiou, G. Mata Martinez, M. Deblas, J. Gomez-Alonso, J. Gonzalez, A. Klinakis, S. Lowe, N. Malats, L. Martinez, J.L. MartinezTorrecuadrada, M. Perez Martinez, M. Ricote, M. Blasco, and M. Serrano for other valuable contributions; and J. Paramio, P. Martinelli, and M. Marques for comments to the manuscript. We thank E. Batlle and his group for many valuable suggestions. This work was supported, in part, by grants from Spanish Ministry of Economy, Industry and Competitiveness (SAF2016-76377-R), CIBERONC (CB16/12/00453 and CB16/12/00273), and Fundacion Cientifica de la Asociacion Espanola Contra el Cancer. CNIO is supported by Ministerio de Ciencia, Innovacion y Universidades as a Centro de Excelencia Severo Ochoa SEV-2015-0510.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshCell Differentiation es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshEpidermal Growth Factor es_ES
dc.subject.meshGene Expression Profiling es_ES
dc.subject.meshGene Ontology es_ES
dc.subject.meshGene Regulatory Networks es_ES
dc.subject.meshHumans es_ES
dc.subject.meshIntegrin alpha6 es_ES
dc.subject.meshMice, 129 Strain es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMice, Nude es_ES
dc.subject.meshMice, Transgenic es_ES
dc.subject.meshOrganoids es_ES
dc.subject.meshReceptors, Notch es_ES
dc.subject.meshSingle-Cell Analysis es_ES
dc.subject.meshStem Cells es_ES
dc.subject.meshUrothelium es_ES
dc.titleUrothelial organoids originating from Cd49fhigh mouse stem cells display Notch-dependent differentiation capacityes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID31562298es_ES
dc.format.volume10es_ES
dc.format.number1es_ES
dc.format.page4407es_ES
dc.identifier.doi10.1038/s41467-019-12307-1es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderCentro de Investigación Biomédica en Red - CIBERONC (Cáncer) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-019-12307-1.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Carcinogénesis Epiteliales_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2016-76377-Res_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/CB16/12/00453es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/CB16/12/00273es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SEV-2015-0510es_ES
dc.rights.accessRightsopen accesses_ES


Ficheros en el ítem

Acceso Abierto
Thumbnail
Acceso Abierto
Acceso Abierto
Thumbnail
Acceso Abierto
Acceso Abierto
Acceso Abierto
Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Atribución-NoComercial-CompartirIgual 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución-NoComercial-CompartirIgual 4.0 Internacional