TY - JOUR
T1 - Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid
AU - Lehmann, Guillermo L.
AU - Hanke-Gogokhia, Christin
AU - Hu, Yang
AU - Bareja, Rohan
AU - Salfati, Zelda
AU - Ginsberg, Michael
AU - Nolan, Daniel J.
AU - Mendez-Huergo, Santiago P.
AU - Dalotto-Moreno, Tomas
AU - Wojcinski, Alexandre
AU - Ochoa, Francisca
AU - Zeng, Shemin
AU - Cerliani, Juan P.
AU - Panagis, Lampros
AU - Zager, Patrick J.
AU - Mullins, Robert F.
AU - Ogura, Shuntaro
AU - Lutty, Gerard A.
AU - Bang, Jakyung
AU - Zippin, Jonathan H.
AU - Romano, Carmelo
AU - Rabinovich, Gabriel A.
AU - Elemento, Olivier
AU - Joyner, Alexandra L.
AU - Rafii, Shahin
AU - Rodriguez-Boulan, Enrique
AU - Benedicto, Ignacio
N1 - Publisher Copyright:
© 2020 Lehmann et al.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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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U2 - 10.1084/jem.20190730
DO - 10.1084/jem.20190730
M3 - Article
C2 - 32196081
AN - SCOPUS:85082147931
SN - 0022-1007
VL - 217
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
M1 - e20190730
ER -