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

Stem Cell Reports. 2022 Jun 14;17(6):1458-1475. doi: 10.1016/j.stemcr.2022.05.005.


Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) are a promising cell source to treat age-related macular degeneration (AMD). Despite several ongoing clinical studies, a detailed mapping of transient cellular states during in vitro differentiation has not been performed. Here, we conduct single-cell transcriptomic profiling of an hESC-RPE differentiation protocol that has been developed for clinical use. Differentiation progressed through a culture diversification recapitulating early embryonic development, whereby cells rapidly acquired a rostral embryo patterning signature before converging toward the RPE lineage. At intermediate steps, we identified and examined the potency of an NCAM1+ retinal progenitor population and showed the ability of the protocol to suppress non-RPE fates. We demonstrated that the method produces a pure RPE pool capable of maturing further after subretinal transplantation in a large-eyed animal model. Our evaluation of hESC-RPE differentiation supports the development of safe and efficient pluripotent stem cell-based therapies for AMD.

Keywords: Large-eyed model; age-related macular degeneration; cellular profiling and transcriptome; cellular therapy; clinical translation; differentiation protocol dynamics; human embryonic stem cell-derived retinal pigment epithelial cell; retinal progenitor cells; single-cell RNA sequencing; subretinal injection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Human Embryonic Stem Cells*
  • Humans
  • Macular Degeneration* / genetics
  • Macular Degeneration* / therapy
  • Retinal Pigment Epithelium
  • Retinal Pigments


  • Retinal Pigments