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Deep Sc-RNA sequencing decoding the molecular dynamic architecture of the human retina

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Abstract

The human retina serves as a light detector and signals transmission tissue. Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events. Here, we sequenced the mRNA of over 0.6 million single cells from human retinas across six regions at nine different ages. Sixty cell sub-types have been identified from the human mature retinas with unique markers. We revealed regional and age differences of gene expression profiles within the human retina. Cell-cell interaction analysis indicated a rich synaptic connection within the retinal cells. Gene expression regulon analysis revealed the specific expression of transcription factors and their regulated genes in human retina cell types. Some of the gene’s expression, such as DKK3, are elevated in aged retinas. A further functional investigation suggested that over expression of DKK3 could impact mitochondrial stability. Overall, decoding the molecular dynamic architecture of the human retina improves our understanding of the vision system.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81790643, 81970839, 82271105, 82121003), the Sichuan Science and Technology Program (2021YFS0033, 2021YFS0369, 2021YFS0404, 2021JDGD0036) and the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2019-I2M-5-032).

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Authors and Affiliations

  1. The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610075, China

    Lulin Huang, Runze Li, Lin Ye, Shanshan Zhang, Huaping Tian, Mingyan Du, Shujin Li, Mu Yang, Guo Huang, Ling Zhong, Yi Shi, Houbin Zhang & Zhenglin Yang

  2. Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, 610075, China

    Lulin Huang & Zhenglin Yang

  3. Department of Ophthalmology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610075, China

    Chao Qu, Jie Li & Man Yu

  4. School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, 325035, China

    Biao Wu, Ran Chen & Wei Chen

  5. Department of Organ Transplant Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610075, China

    Hongjie Yang

  6. Department of Ophthalmology, Peking University Third Hospital, Beijing, 100730, China

    Changguan Wang

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  1. Lulin Huang
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  2. Runze Li
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  3. Lin Ye
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  7. Chao Qu
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  20. Wei Chen
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  21. Zhenglin Yang
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Correspondence to Zhenglin Yang.

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Huang, L., Li, R., Ye, L. et al. Deep Sc-RNA sequencing decoding the molecular dynamic architecture of the human retina. Sci. China Life Sci. 66, 496–515 (2023). https://doi.org/10.1007/s11427-021-2163-1

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