Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid.
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid.
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DOI：
10.1084/jem.20190730
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发表时间：
2020-06-01
期刊：
影响因子：
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通讯作者：
Benedicto I
中科院分区：
文献类型：
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作者：
Lehmann GL;Hanke-Gogokhia C;Hu Y;Bareja R;Salfati Z;Ginsberg M;Nolan DJ;Mendez-Huergo SP;Dalotto-Moreno T;Wojcinski A;Ochoa F;Zeng S;Cerliani JP;Panagis L;Zager PJ;Mullins RF;Ogura S;Lutty GA;Bang J;Zippin JH;Romano C;Rabinovich GA;Elemento O;Joyner AL;Rafii S;Rodriguez-Boulan E;Benedicto I
作者以单细胞分辨率报告了小鼠视网膜色素上皮/脉络膜组织的转录组。脉络膜内皮细胞的一个子集表达 Indian Hedgehog，其目标是调节肥大细胞存活和损伤后炎症反应的间充质干细胞样细胞。视网膜感光细胞的活性和存活取决于视网膜色素上皮 (RPE) 执行的支持功能以及下方脉络膜血管输送的氧气和营养物质。通过结合单细胞和批量 RNA 测序，我们对小鼠 RPE/脉络膜细胞类型进行了分类，并表征了脉络膜内皮细胞的组织特异性转录组特征。我们发现邻近 RPE 的脉络膜内皮表达高水平的 Indian Hedgehog，并确定其下游靶标为基质 GLI1+ 间充质干细胞样细胞。 Hedgehog信号传导的体内遗传损伤导致脉络膜肥大细胞显着损失，以及视网膜损伤后炎症反应的改变和视觉功能缺陷的加剧。我们的研究揭示了成人 RPE/脉络膜的细胞和分子景观，并揭示了 Hedgehog 调节的脉络膜免疫调节信号通路。这些结果为视网膜血管疾病和脉络膜相关炎症致盲疾病的研究和治疗开辟了新途径。
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.
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影响因子：
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作者：
Caughey, George H.
通讯作者：
Caughey, George H.
影响因子：
23.9
作者：
Brownell, Isaac;Guevara, Elizabeth;Bai, C. Brian;Loomis, Cynthia A.;Joyner, Alexandra L.
通讯作者：
Joyner, Alexandra L.
影响因子：
2.7
作者：
Dakubo, Gabriel D.;Mazerolle, Chantal;Wallace, Valerie A.
通讯作者：
Wallace, Valerie A.
DOI：
10.1073/pnas.1616447113
发表时间：
2016-11-22
影响因子：
11.1
作者：
Lee, John J.;Rothenberg, Michael E.;Beachy, Philip A.
通讯作者：
Beachy, Philip A.
影响因子：
30.5
作者：
通讯作者：
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