Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid
- Autores
- Lehmann Mantaras, Guillermo Luis; Hanke Gogokhia, Christin; Hu, Yang; Bareja, Rohan; Salfati, Zelda; Ginsberg, Michael; Nolan, Daniel J.; Mendez Huergo, Santiago Patricio; D'alotto Moreno, Tomas; Wojcinski, Alexandre; Ochoa, Francisca; Zeng, Shemin; Cerliani, Juan Pablo; Panagis, Lampros; Zager, Patrick J.; Mullins, Robert F.; Ogura, Shuntaro; Lutty, Gerard A.; Bang, Jakyung; Zippin, Jonathan H.; Romano, Carmelo; Rabinovich, Gabriel Adrián; Elemento, Olivier; Joyner, Alexandra L.; Rafii, Shahin; Rodriguez Boulan, Enrique; Benedicto, Ignacio
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Lehmann Mantaras, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados Unidos. Regeneron Pharmaceuticals; Estados Unidos
Fil: Hanke Gogokhia, Christin. Cornell University; Estados Unidos
Fil: Hu, Yang. Cornell University; Estados Unidos
Fil: Bareja, Rohan. Cornell University; Estados Unidos
Fil: Salfati, Zelda. Cornell University; Estados Unidos
Fil: Ginsberg, Michael. Angiocrine Bioscience; Estados Unidos
Fil: Nolan, Daniel J.. Angiocrine Bioscience; Estados Unidos
Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Wojcinski, Alexandre. Memorial Sloan-kettering Cancer Center.; Estados Unidos
Fil: Ochoa, Francisca. Regeneron Pharmaceuticals; Estados Unidos
Fil: Zeng, Shemin. University of Iowa; Estados Unidos
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Panagis, Lampros. Regeneron Pharmaceuticals; Estados Unidos
Fil: Zager, Patrick J.. Cornell University; Estados Unidos
Fil: Mullins, Robert F.. University of Iowa; Estados Unidos
Fil: Ogura, Shuntaro. University Johns Hopkins; Estados Unidos
Fil: Lutty, Gerard A.. University Johns Hopkins; Estados Unidos
Fil: Bang, Jakyung. Cornell University; Estados Unidos
Fil: Zippin, Jonathan H.. Columbia University; Estados Unidos. Cornell University; Estados Unidos
Fil: Romano, Carmelo. Regeneron Pharmaceuticals; Estados Unidos
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Elemento, Olivier. Cornell University; Estados Unidos
Fil: Joyner, Alexandra L.. Memorial Sloan-kettering Cancer Center.; Estados Unidos
Fil: Rafii, Shahin. Cornell University; Estados Unidos
Fil: Rodriguez Boulan, Enrique. Cornell University; Estados Unidos
Fil: Benedicto, Ignacio. Cornell University; Estados Unidos. Minsterio de Ciencia e Innovación. Centro Nacional de Investigaciones Cardiovasculares; España - Materia
-
ENDOTHELIAL
RETINAL
CHOROID
INDIAN HEDGEHOG - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/110228
Ver los metadatos del registro completo
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Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroidLehmann Mantaras, Guillermo LuisHanke Gogokhia, ChristinHu, YangBareja, RohanSalfati, ZeldaGinsberg, MichaelNolan, Daniel J.Mendez Huergo, Santiago PatricioD'alotto Moreno, TomasWojcinski, AlexandreOchoa, FranciscaZeng, SheminCerliani, Juan PabloPanagis, LamprosZager, Patrick J.Mullins, Robert F.Ogura, ShuntaroLutty, Gerard A.Bang, JakyungZippin, Jonathan H.Romano, CarmeloRabinovich, Gabriel AdriánElemento, OlivierJoyner, Alexandra L.Rafii, ShahinRodriguez Boulan, EnriqueBenedicto, IgnacioENDOTHELIALRETINALCHOROIDINDIAN HEDGEHOGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The 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.Fil: Lehmann Mantaras, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados Unidos. Regeneron Pharmaceuticals; Estados UnidosFil: Hanke Gogokhia, Christin. Cornell University; Estados UnidosFil: Hu, Yang. Cornell University; Estados UnidosFil: Bareja, Rohan. Cornell University; Estados UnidosFil: Salfati, Zelda. Cornell University; Estados UnidosFil: Ginsberg, Michael. Angiocrine Bioscience; Estados UnidosFil: Nolan, Daniel J.. Angiocrine Bioscience; Estados UnidosFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Wojcinski, Alexandre. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Ochoa, Francisca. Regeneron Pharmaceuticals; Estados UnidosFil: Zeng, Shemin. University of Iowa; Estados UnidosFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Panagis, Lampros. Regeneron Pharmaceuticals; Estados UnidosFil: Zager, Patrick J.. Cornell University; Estados UnidosFil: Mullins, Robert F.. University of Iowa; Estados UnidosFil: Ogura, Shuntaro. University Johns Hopkins; Estados UnidosFil: Lutty, Gerard A.. University Johns Hopkins; Estados UnidosFil: Bang, Jakyung. Cornell University; Estados UnidosFil: Zippin, Jonathan H.. Columbia University; Estados Unidos. Cornell University; Estados UnidosFil: Romano, Carmelo. Regeneron Pharmaceuticals; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Elemento, Olivier. Cornell University; Estados UnidosFil: Joyner, Alexandra L.. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Rafii, Shahin. Cornell University; Estados UnidosFil: Rodriguez Boulan, Enrique. Cornell University; Estados UnidosFil: Benedicto, Ignacio. Cornell University; Estados Unidos. Minsterio de Ciencia e Innovación. Centro Nacional de Investigaciones Cardiovasculares; EspañaRockefeller University Press2020-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/110228Lehmann Mantaras, Guillermo Luis; Hanke Gogokhia, Christin; Hu, Yang; Bareja, Rohan; Salfati, Zelda; et al.; Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid; Rockefeller University Press; Journal of Experimental Medicine; 217; 6; 6-2020; 1-210022-1007CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://rupress.org/jem/article/doi/10.1084/jem.20190730/151573/Singlecell-profiling-reveals-aninfo:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20190730info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:43Zoai:ri.conicet.gov.ar:11336/110228instacron: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:34982025-09-29 09:32:43.838CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid |
| title |
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid |
| spellingShingle |
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid Lehmann Mantaras, Guillermo Luis ENDOTHELIAL RETINAL CHOROID INDIAN HEDGEHOG |
| title_short |
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid |
| title_full |
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid |
| title_fullStr |
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid |
| title_full_unstemmed |
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid |
| title_sort |
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid |
| dc.creator.none.fl_str_mv |
Lehmann Mantaras, Guillermo Luis Hanke Gogokhia, Christin Hu, Yang Bareja, Rohan Salfati, Zelda Ginsberg, Michael Nolan, Daniel J. Mendez Huergo, Santiago Patricio D'alotto Moreno, Tomas Wojcinski, Alexandre Ochoa, Francisca Zeng, Shemin Cerliani, Juan Pablo Panagis, Lampros Zager, Patrick J. Mullins, Robert F. Ogura, Shuntaro Lutty, Gerard A. Bang, Jakyung Zippin, Jonathan H. Romano, Carmelo Rabinovich, Gabriel Adrián Elemento, Olivier Joyner, Alexandra L. Rafii, Shahin Rodriguez Boulan, Enrique Benedicto, Ignacio |
| author |
Lehmann Mantaras, Guillermo Luis |
| author_facet |
Lehmann Mantaras, Guillermo Luis Hanke Gogokhia, Christin Hu, Yang Bareja, Rohan Salfati, Zelda Ginsberg, Michael Nolan, Daniel J. Mendez Huergo, Santiago Patricio D'alotto Moreno, Tomas Wojcinski, Alexandre Ochoa, Francisca Zeng, Shemin Cerliani, Juan Pablo Panagis, Lampros Zager, Patrick J. Mullins, Robert F. Ogura, Shuntaro Lutty, Gerard A. Bang, Jakyung Zippin, Jonathan H. Romano, Carmelo Rabinovich, Gabriel Adrián Elemento, Olivier Joyner, Alexandra L. Rafii, Shahin Rodriguez Boulan, Enrique Benedicto, Ignacio |
| author_role |
author |
| author2 |
Hanke Gogokhia, Christin Hu, Yang Bareja, Rohan Salfati, Zelda Ginsberg, Michael Nolan, Daniel J. Mendez Huergo, Santiago Patricio D'alotto Moreno, Tomas Wojcinski, Alexandre Ochoa, Francisca Zeng, Shemin Cerliani, Juan Pablo Panagis, Lampros Zager, Patrick J. Mullins, Robert F. Ogura, Shuntaro Lutty, Gerard A. Bang, Jakyung Zippin, Jonathan H. Romano, Carmelo Rabinovich, Gabriel Adrián Elemento, Olivier Joyner, Alexandra L. Rafii, Shahin Rodriguez Boulan, Enrique Benedicto, Ignacio |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ENDOTHELIAL RETINAL CHOROID INDIAN HEDGEHOG |
| topic |
ENDOTHELIAL RETINAL CHOROID INDIAN HEDGEHOG |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
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. Fil: Lehmann Mantaras, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados Unidos. Regeneron Pharmaceuticals; Estados Unidos Fil: Hanke Gogokhia, Christin. Cornell University; Estados Unidos Fil: Hu, Yang. Cornell University; Estados Unidos Fil: Bareja, Rohan. Cornell University; Estados Unidos Fil: Salfati, Zelda. Cornell University; Estados Unidos Fil: Ginsberg, Michael. Angiocrine Bioscience; Estados Unidos Fil: Nolan, Daniel J.. Angiocrine Bioscience; Estados Unidos Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Wojcinski, Alexandre. Memorial Sloan-kettering Cancer Center.; Estados Unidos Fil: Ochoa, Francisca. Regeneron Pharmaceuticals; Estados Unidos Fil: Zeng, Shemin. University of Iowa; Estados Unidos Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Panagis, Lampros. Regeneron Pharmaceuticals; Estados Unidos Fil: Zager, Patrick J.. Cornell University; Estados Unidos Fil: Mullins, Robert F.. University of Iowa; Estados Unidos Fil: Ogura, Shuntaro. University Johns Hopkins; Estados Unidos Fil: Lutty, Gerard A.. University Johns Hopkins; Estados Unidos Fil: Bang, Jakyung. Cornell University; Estados Unidos Fil: Zippin, Jonathan H.. Columbia University; Estados Unidos. Cornell University; Estados Unidos Fil: Romano, Carmelo. Regeneron Pharmaceuticals; Estados Unidos Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina Fil: Elemento, Olivier. Cornell University; Estados Unidos Fil: Joyner, Alexandra L.. Memorial Sloan-kettering Cancer Center.; Estados Unidos Fil: Rafii, Shahin. Cornell University; Estados Unidos Fil: Rodriguez Boulan, Enrique. Cornell University; Estados Unidos Fil: Benedicto, Ignacio. Cornell University; Estados Unidos. Minsterio de Ciencia e Innovación. Centro Nacional de Investigaciones Cardiovasculares; España |
| description |
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. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020-06 |
| 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/11336/110228 Lehmann Mantaras, Guillermo Luis; Hanke Gogokhia, Christin; Hu, Yang; Bareja, Rohan; Salfati, Zelda; et al.; Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid; Rockefeller University Press; Journal of Experimental Medicine; 217; 6; 6-2020; 1-21 0022-1007 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/110228 |
| identifier_str_mv |
Lehmann Mantaras, Guillermo Luis; Hanke Gogokhia, Christin; Hu, Yang; Bareja, Rohan; Salfati, Zelda; et al.; Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid; Rockefeller University Press; Journal of Experimental Medicine; 217; 6; 6-2020; 1-21 0022-1007 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
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info:eu-repo/semantics/altIdentifier/url/https://rupress.org/jem/article/doi/10.1084/jem.20190730/151573/Singlecell-profiling-reveals-an info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20190730 |
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Rockefeller University Press |
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Rockefeller University Press |
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