Identifying Biomarkers of Retinal Pigment Epithelial Cell Stem Cell-derived RPE Cell Heterogeneity and Transplantation Efficacy

• Published in: bioRxiv
• Main Authors: Farjood, Farhad, Manos, Justine D, Wang, Yue, Williams, Anne L, Zhao, Cuiping, Borden, Susan, Alam, Nazia, Prusky, Glen, Temple, Sally, Stern, Jeffrey H, Boles, Nathan C
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 23.11.2022
• Subjects: Age; Gene expression; Integration; Macular degeneration; Retina; Retinal degeneration; Retinal pigment epithelium; Stem cells; Transplantation
• DOI: 10.1101/2022.11.22.517447

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.Footnotes* https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE211189