Journal
STEM CELL REPORTS
Volume 17, Issue 6, Pages 1458-1475Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2022.05.005
Keywords
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Categories
Funding
- Swedish Research Council
- Ragnar Soderberg Foundation
- MingWai Lau Center for Reparative Medicine
- Center for Innovative Medicine
- Wallenberg Academy Fellow
- Strategic Research Area Stem Cells and Regenerative Medicine
- Vinnova
- Stockholm County Council (ALF project)
- Karolinska Institutet
- Crown Princess Margareta's Foundation for the Visually Impaired
- ARMEC Lindeberg Foundation
- Ulla och Ingemar Dahlberg Foundation
- King Gustav V and Queen Victoria Foundation
- Compton Foundation
- Swiss National Science Foundation [CRSK-3_190495, PZ00P3_193445]
- Chan Zuckerberg Initiative [CZF2019002427]
- Knut and Alice Wallenberg Foundation
- Centre for Innovative Medicine
- Jonasson donation
- KI/SLL
- board of research at the KI
- research committee at the Karolinska Hospital
- Swiss National Science Foundation (SNF) [CRSK-3_190495, PZ00P3_193445] Funding Source: Swiss National Science Foundation (SNF)
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This study conducted single-cell transcriptomic profiling of an hESC-RPE differentiation protocol for treating AMD and found that the cells exhibited characteristics of early embryonic development during differentiation, ultimately obtaining a pure RPE cell population. The findings of this study are significant for the development of safe and effective pluripotent stem cell-based therapies for AMD.
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.
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