Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid | Zendy

Guillermo L. Lehmann | Zendy; Christin HankeGogokhia | Zendy; Yang Hu | Zendy; Rohan Bareja | Zendy; Zelda Salfati | Zendy; Michael Ginsberg | Zendy; Daniel J. Nolan | Zendy; Santiago P. MéndezHuergo | Zendy; Tomás DalottoMoreno | Zendy; Alexandre Wojcinski | Zendy; Francisca Ochoa | Zendy; Shemin Zeng | Zendy; Juan P. Cerliani | Zendy; Lampros Panagis | Zendy; Patrick J. Zager | Zendy; Robert F. Mullins | Zendy; Shuntaro Ogura | Zendy; Gerard A. Lutty | Zendy; Jakyung Bang | Zendy; Jonathan H. Zippin | Zendy; Carmelo Romano | Zendy; Gabriel A. Rabinovich | Zendy; Olivier Elemento | Zendy; Alexandra L. Joyner | Zendy; Shahin Rafii | Zendy; Enrique RodriguezBoulan | Zendy; Ignacio Benedicto | Zendy

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Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid

Author(s) -

Guillermo L. Lehmann,

Christin HankeGogokhia,

Yang Hu,

Rohan Bareja,

Zelda Salfati,

Michael Ginsberg,

Daniel J. Nolan,

Santiago P. MéndezHuergo,

Tomás DalottoMoreno,

Alexandre Wojcinski,

Francisca Ochoa,

Shemin Zeng,

Juan P. Cerliani,

Lampros Panagis,

Patrick J. Zager,

Robert F. Mullins,

Shuntaro Ogura,

Gerard A. Lutty,

Jakyung Bang,

Jonathan H. Zippin,

Carmelo Romano,

Gabriel A. Rabinovich,

Olivier Elemento,

Alexandra L. Joyner,

Shahin Rafii,

Enrique RodriguezBoulan,

Ignacio Benedicto

Publication year - 2020

Publication title -

the journal of experimental medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 8.483

H-Index - 448

eISSN - 1540-9538

pISSN - 0022-1007

DOI - 10.1084/jem.20190730

Subject(s) - choroid , retinal pigment epithelium , biology , microbiology and biotechnology , gli1 , hedgehog , retinal , mesenchymal stem cell , transcriptome , endothelial stem cell , hedgehog signaling pathway , stem cell , stromal cell , retina , pathology , medicine , signal transduction , cancer research , neuroscience , genetics , in vitro , gene , gene expression , biochemistry

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.

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