Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells.
Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells.
复制标题
鉴定视网膜色素上皮细胞异质性和移植功效的生物标志物。
DOI：
10.1084/jem.20230913
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Boles,NathanC
中科院分区：
文献类型：
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作者：
Farjood,Farhad;Manos,JustineD;Wang,Yue;Williams,AnneL;Zhao,Cuiping;Borden,Susan;Alam,Nazia;Prusky,Glen;Temple,Sally;Stern,JeffreyH;Boles,NathanC
Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell–derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.
