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

Hani Jieun Kim; Michelle O'Hara-Wright; Daniel Kim; To Ha Loi; Benjamin Y Lim; Robyn V Jamieson; Anai Gonzalez-Cordero; Pengyi Yang

doi:10.1016/j.stemcr.2022.12.002

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

Stem Cell Reports. 2023 Jan 10;18(1):175-189. doi: 10.1016/j.stemcr.2022.12.002.

Authors

Hani Jieun Kim¹, Michelle O'Hara-Wright², Daniel Kim³, To Ha Loi⁴, Benjamin Y Lim⁵, Robyn V Jamieson⁶, Anai Gonzalez-Cordero⁷, Pengyi Yang⁸

Affiliations

¹ Computational Systems Biology Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia; School of Mathematics and Statistics, The University of Sydney, Sydney, NSW 2006, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.
² School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia; Stem Cell Medicine Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
³ Computational Systems Biology Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.
⁴ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia; Eye Genetics Research Unit, Children's Medical Research Institute, Sydney Children's Hospitals Network, Save Sight Institute, The University of Sydney, Westmead, NSW 2145, Australia.
⁵ Stem Cell Medicine Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
⁶ Specialty of Genomic Medicine, Faculty of Medicine and Health, University of Sydney, Westmead, NSW 2145, Australia; Eye Genetics Research Unit, Children's Medical Research Institute, Sydney Children's Hospitals Network, Save Sight Institute, The University of Sydney, Westmead, NSW 2145, Australia.
⁷ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia; Stem Cell Medicine Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia. Electronic address: agonzalez-cordero@cmri.org.au.
⁸ Computational Systems Biology Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia; School of Mathematics and Statistics, The University of Sydney, Sydney, NSW 2006, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia. Electronic address: pengyi.yang@sydney.edu.au.

Abstract

Characterizing cell identity in complex tissues such as the human retina is essential for studying its development and disease. While retinal organoids derived from pluripotent stem cells have been widely used to model development and disease of the human retina, there is a lack of studies that have systematically evaluated the molecular and cellular fidelity of the organoids derived from various culture protocols in recapitulating their in vivo counterpart. To this end, we performed an extensive meta-atlas characterization of cellular identities of the human eye, covering a wide range of developmental stages. The resulting map uncovered previously unknown biomarkers of major retinal cell types and those associated with cell-type-specific maturation. Using our retinal-cell-identity map from the fetal and adult tissues, we systematically assessed the fidelity of the retinal organoids in mimicking the human eye, enabling us to comprehensively benchmark the current protocols for retinal organoid generation.

Keywords: cell identity; eye; fidelity; human eye; maturation; pluripotent stem cells; retina; retinal organoids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cell Differentiation
Humans
Induced Pluripotent Stem Cells* / metabolism
Neurons
Organoids
Pluripotent Stem Cells* / metabolism
Retina / metabolism