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dc.contributor.author | Lehmann, Guillermo L | |
dc.contributor.author | Hanke-Gogokhia, Christin | |
dc.contributor.author | Hu, Yang | |
dc.contributor.author | Bareja, Rohan | |
dc.contributor.author | Salfati, Zelda | |
dc.contributor.author | Ginsberg, Michael | |
dc.contributor.author | Nolan, Daniel J | |
dc.contributor.author | Mendez-Huergo, Santiago P | |
dc.contributor.author | Dalotto-Moreno, Tomas | |
dc.contributor.author | Wojcinski, Alexandre | |
dc.contributor.author | Ochoa, Francisca | |
dc.contributor.author | Zeng, Shemin | |
dc.contributor.author | Cerliani, Juan P | |
dc.contributor.author | Panagis, Lampros | |
dc.contributor.author | Zager, Patrick J | |
dc.contributor.author | Mullins, Robert F | |
dc.contributor.author | Ogura, Shuntaro | |
dc.contributor.author | Lutty, Gerard A | |
dc.contributor.author | Bang, Jakyung | |
dc.contributor.author | Zippin, Jonathan H | |
dc.contributor.author | Romano, Carmelo | |
dc.contributor.author | Rabinovich, Gabriel A | |
dc.contributor.author | Elemento, Olivier | |
dc.contributor.author | Joyner, Alexandra L | |
dc.contributor.author | Rafii, Shahin | |
dc.contributor.author | Rodriguez-Boulan, Enrique | |
dc.contributor.author | Benedicto, Ignacio | |
dc.date.accessioned | 2020-03-25T12:37:10Z | |
dc.date.available | 2020-03-25T12:37:10Z | |
dc.date.issued | 2020-06-01 | |
dc.identifier.citation | J Exp Med. 2020; 217(6):e20190730 | es_ES |
dc.identifier.issn | 0022-1007 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9328 | |
dc.description.abstract | The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single-cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. We found that choroidal endothelium adjacent to the RPE expresses high levels of Indian Hedgehog and identified its downstream target as stromal GLI1+ mesenchymal stem cell-like cells. In vivo genetic impairment of Hedgehog signaling induced significant loss of choroidal mast cells, as well as an altered inflammatory response and exacerbated visual function defects after retinal damage. Our studies reveal the cellular and molecular landscape of adult RPE/choroid and uncover a Hedgehog-regulated choroidal immunomodulatory signaling circuit. These results open new avenues for the study and treatment of retinal vascular diseases and choroid-related inflammatory blinding disorders. | es_ES |
dc.description.sponsorship | Funding for this study was provided by National Institutes of Health grants EY08538 and GM34107 (E. Rodriguez-Boulan); EY027038 (R.F. Mullins); 1R21CA224391-01A1 (J.H. Zippin); and 1R01CA194547, 1U24CA210989, and P50CA211024 (O. Elemento); National Cancer Institute grant R01CA192176 and cancer center support grant P30 CA008748-48 (A.L. Joyner); Comunidad Autónoma de Madrid grant 2017-T1/BMD-5247 (I. Benedicto); Agencia Nacional Argentina de Promoción Cient´ıfica y Tecnológica grant PICT 2014-3687 and Fundación Sales (G.A. Rabinovich); a Pew Latin American Fellowship (G.L. Lehmann); Calder Research Scholar Award Vitiligo/Pigment Cell Disorders (J.H. Zippin); Starr Foundation Tri-Institutional Stem Cell Initiative award 2013-028; NYSTEM contract C32596GG; and Research to Prevent Blindness and Dyson Foundation departmental grants. The CNIC is supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Rockefeller University Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 32196081 | es_ES |
dc.format.volume | 217 | es_ES |
dc.format.number | 6 | es_ES |
dc.identifier.doi | 10.1084/jem.20190730 | es_ES |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | |
dc.contributor.funder | NIH - National Cancer Institute (NCI) (Estados Unidos) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.contributor.funder | Agencia Nacional de Promoción Científica y Tecnológica (Argentina) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1540-9538 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1084/jem.20190730 | es_ES |
dc.identifier.journal | The Journal of experimental medicine | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genética | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.rights.accessRights | open access | es_ES |