Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues  

作　　者：Jian Wu Chaoye Wang Shuhui Sun Tianmin Ren Lijie Pan Hongyi Liu Simeng Hou Shen Wu Xuejing Yan Jingxue Zhang Xiaofang Zhao Weihai Liu Sirui Zhu Shuwen Wei Chi Zhang Xu Jia Qi Zhang Ziyu Yu Yehong Zhuo Qi Zhao Chenlong Yang Ningli Wang 

机构地区：[1]Beijing Institute of Ophthalmology,Beijing Tongren Eye Center,Beijing Tongren Hospital,Capital Medical University,Beijing Key Laboratory of Ophthalmology and Visual Sciences,Beijing 100730,China [2]State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangzhou 510060,China [3]State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University Cancer Center,Guangzhou 510060,China [4]State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [5]Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China [6]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China [7]Department of Neurosurgery,Peking University Third Hospital,Center for Precision Neurosurgery and Oncology of Peking University Health Science Center,Beijing 100191,China [8]Spencer Center for Vision Research,Byers Eye Institute,School of Medicine,Stanford University,Palo Alto,CA 94304,USA

出　　处：《Protein & Cell》2024年第8期594-611,共18页蛋白质与细胞（英文版）

基　　金：supported by Beijing Traditional Chinese Medicine Technology Development Fund Project(J2018-50 to C.L.);the National Natural Science Foundation of China(81901202 to C.Y.);Beijing Natural Science Foundation(7222217 to C.Y.);the Capital Health Research and Development of Special(2022-4-40918 to C.Y.);Clinical Medicine Plus X-Young Scholars Project,Peking University,the Fundamental Research Funds for the Central Universities(PKU2021LCXQ007 to C.Y.).

摘　　要：The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle glaucoma.However,the molecular basis and biological significance of the aging process in TM have not been fully elucidated.Here,we established a dynamic single-cell transcriptomic landscape of aged macaque TM,wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging.Furthermore,we divided TM cells into 13 clusters and performed an in-depth analysis on cluster O,which had the highest aging score and the most significant changes in cell proportions between the two groups.Ultimately,we found that the APOE gene was an important differentially expressed gene in cluster O during the aging process,highlighting the close relationship between cell migration and extracellular matrix regulation,and TM function.Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components,thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range.Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

关 键 词：single-cell transcriptomic atlas MACAQUE trabecular meshwork ocular outflow tissue aging 

分 类 号：R764[医药卫生—耳鼻咽喉科]