PT  - JOURNAL ARTICLE
AU  - Farhad Farjood
AU  - Justine D. Manos
AU  - Yue Wang
AU  - Anne L. Williams
AU  - Cuiping Zhao
AU  - Susan Borden
AU  - Nazia Alam
AU  - Glen Prusky
AU  - Sally Temple
AU  - Jeffrey H. Stern
AU  - Nathan C. Boles
TI  - Identifying Biomarkers of Retinal Pigment Epithelial Cell Stem Cell-derived RPE Cell Heterogeneity and Transplantation Efficacy
AID  - 10.1101/2022.11.22.517447
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.22.517447
4099  - http://biorxiv.org/content/early/2022/11/23/2022.11.22.517447.short
4100  - http://biorxiv.org/content/early/2022/11/23/2022.11.22.517447.full
AB  - 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 (sc-RNA-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 a 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.Competing Interest StatementThe authors have declared no competing interest.