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bioRxiv · 10.1101/2022.11.22.517447

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

Farjood, F.·Manos, J. D.·Wang, Y.·Williams, A. L.·Zhao, C.·Borden, S.·Alam, N.·Prusky, G.·Temple, S.·Stern, J. H.·Boles, N. C.
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Abstract

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.

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Farjood, F., Manos, J. D., Wang, Y., Williams, A. L., Zhao, C., Borden, S., Alam, N., Prusky, G., Temple, S., Stern, J. H., Boles, N. C.. 2022-11-23. Identifying Biomarkers of Retinal Pigment Epithelial Cell Stem Cell-derived RPE Cell Heterogeneity and Transplantation Efficacy. https://doi.org/10.1101/2022.11.22.517447

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