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

Autor: Jakyung Bang, Shuntaro Ogura, Jonathan H. Zippin, Lampros Panagis, Yang Hu, Alexandre Wojcinski, Daniel J. Nolan, Olivier Elemento, Ignacio Benedicto, Zelda Salfati, Christin Hanke-Gogokhia, Michael Ginsberg, Gerard A. Lutty, Santiago P. Méndez-Huergo, Enrique Rodriguez-Boulan, Francisca Ochoa, Patrick J. Zager, Tomás Dalotto-Moreno, Carmelo Romano, Gabriel A. Rabinovich, Guillermo L. Lehmann, Alexandra L. Joyner, Juan P. Cerliani, Robert F. Mullins, Shahin Rafii, Rohan Bareja, Shemin Zeng
Přispěvatelé: National Institutes of Health (Estados Unidos), NIH - National Cancer Institute (NCI) (Estados Unidos), Comunidad de Madrid (España), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Fundación ProCNIC, Agencia Nacional de Promoción Científica y Tecnológica (Argentina)
Rok vydání: 2020
Předmět:
0301 basic medicine
Transcription
Genetic
INDIAN HEDGEHOG
Innate immunity and inflammation
CHOROID
Retinal Pigment Epithelium
chemistry.chemical_compound
0302 clinical medicine
Immunology and Allergy
Mast Cells
biology
Patología
purl.org/becyt/ford/3.1 [https]
Hedgehog signaling pathway
Cell biology
Medicina Básica
medicine.anatomical_structure
Organ Specificity
Melanocytes
RETINAL
purl.org/becyt/ford/3 [https]
Single-Cell Analysis
Signal Transduction
Cell type
CIENCIAS MÉDICAS Y DE LA SALUD
Indian hedgehog
Stromal cell
Endothelium
Immunology
Zinc Finger Protein GLI1
Article
Immunomodulation
03 medical and health sciences
Cardiovascular Biology
medicine
Animals
Hedgehog Proteins
Cell Proliferation
Inflammation
ENDOTHELIAL
Retinal pigment epithelium
Choroid
Endothelial Cells
Retinal
biology.organism_classification
eye diseases
Mice
Inbred C57BL
030104 developmental biology
Gene Expression Regulation
chemistry
030221 ophthalmology & optometry
sense organs
Zdroj: Repisalud
Instituto de Salud Carlos III (ISCIII)
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
Popis: The authors report the transcriptome of mouse retinal pigment epithelium/choroid tissue at single-cell resolution. A subset of choroidal endothelial cells expresses Indian Hedgehog, which targets mesenchymal stem cell–like cells regulating mast cell survival and the inflammatory response after damage.
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.
Graphical Abstract
Databáze: OpenAIRE
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