Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation

Petrus‐Reurer, Sandra; Lederer, Alex R; Baqué-Vidal, Laura; Douagi, Iyadh; Pannagel, Belinda; Khven, Irina; Aronsson, Monica; Bartuma, Hammurabi; Wagner, Magdalena; Wrona, Andreas; Efstathopoulos, Paschalis; Jaberi, Elham; Willenbrock, Hanni; Shimizu, Yutaka; Villaescusa, J. Carlos; André, Helder; Sundström, Erik; Bhaduri, Aparna; Kriegstein, Arnold R.; Kvanta, Anders; Manno, Gioele La; Lanner, Fredrik

doi:10.1016/j.stemcr.2022.05.005

Cited by 20 publications

(12 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, none of the protocols can currently generate retinal pigment epithelium (RPEs), which is a clear shortcoming of the protocols. Future benchmarking efforts will require the incorporation of studies that generate single-cell transcriptomic profiles of RPEs across development ( Hu et al., 2019 ; Petrus-Reurer et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

et al. 2023

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

et al. 2023

View full text Add to dashboard Cite

“…Our present transcriptomic analysis demonstrated an incomplete ability to separate the RPE cell transcriptomic profiles based solely on time, pointing out the need to dissect RPE cellular heterogeneity at each time point. Recent studies using single-cell approaches have reported multiple RPE subpopulations within the stem cell–derived, native human and mouse RPE with unique transcriptional and morphological characteristics, indicating that the RPE cell layer is composed of heterogeneous cell populations that may have differing functional and clinical capabilities ( Lee et al, 2022 ; Petrus-Reurer et al, 2022 ; Voigt et al, 2019 ; Xu et al, 2021 ). Identification of the subpopulations responsible for vision rescue can improve regulatory evaluation and improve RPE cell products to result in better transplantation outcomes.…”

Section: Discussionmentioning

confidence: 99%

Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells

Farjood,

Manos,

Wang

et al. 2023

Journal of Experimental Medicine

View full text Add to dashboard Cite

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.

show abstract

“…Our present transcriptomic analysis demonstrated an incomplete ability to separate the RPE cell transcriptomic profiles based solely on time, pointing out the need to dissect RPE cellular heterogeneity at each timepoint. Recent studies using single cell approaches have reported multiple RPE subpopulations within the stem cell-derived, native human and mouse RPE with unique transcriptional and morphological characteristics, indicating that the RPE cell layer is composed of heterogenous cell populations that may have differing functional and clinical capabilities (Lee et al, 2022; Petrus-Reurer et al, 2022; Voigt et al, 2019; Xu et al, 2021). Identification of the subpopulations responsible for vision rescue can improve regulatory evaluation and improve RPE cell products to result in better transplantation outcomes.…”

Section: Discussionmentioning

confidence: 99%

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

Farjood

Manos²,

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation

Cited by 20 publications

References 38 publications

Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells

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

Contact Info

Product

Resources

About