Dynamic human retinal pigment epithelium (RPE) and choroid architecture based on single-cell transcriptomic landscape analysis

Lulin Huang; Lin Ye; Runze Li; Shanshan Zhang; Chao Qu; Shujin Li; Jie Li; Mu Yang; Biao Wu; Ran Chen; Guo Huang; Bo Gong; Zheng Li; Hongjie Yang; Man Yu; Yi Shi; Changguan Wang; Wei Chen; Zhenglin Yang

doi:10.1016/j.gendis.2022.11.007

Dynamic human retinal pigment epithelium (RPE) and choroid architecture based on single-cell transcriptomic landscape analysis

Genes Dis. 2022 Dec 15;10(6):2540-2556. doi: 10.1016/j.gendis.2022.11.007. eCollection 2023 Nov.

Authors

Lulin Huang^{1

2}, Lin Ye¹, Runze Li¹, Shanshan Zhang¹, Chao Qu³, Shujin Li¹, Jie Li³, Mu Yang¹, Biao Wu⁴, Ran Chen⁴, Guo Huang¹, Bo Gong¹, Zheng Li¹, Hongjie Yang⁵, Man Yu³, Yi Shi¹, Changguan Wang⁶, Wei Chen⁴, Zhenglin Yang^{1

2}

Affiliations

¹ Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
² Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, Sichuan 610072, China.
³ Department of Ophthalmology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
⁴ School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
⁵ Department of Organ Transplant Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
⁶ Department of Ophthalmology, Peking University Third Hospital, Beijing 100730, China.

Abstract

The retinal pigment epithelium (RPE) and choroid are located behind the human retina and have multiple functions in the human visual system. Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies. Here, we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages, revealing regional and age differences within the human RPE and choroid. Cell-cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types. Moreover, the transcription factors and their target genes change during aging. The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level. Moreover, we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging. The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

Keywords: Aging; Choroid; ELN; Human; RPE; scRNA-seq.