Transcriptomics of CD29+/CD44+ cells isolated from hPSC retinal organoids reveals a single cell population with retinal progenitor and Müller glia characteristics

• Published in: Scientific reports Vol. 13; no. 1; p. 5081
• Main Authors: Eastlake, Karen, Luis, Joshua, Wang, Weixin, Lamb, William, Khaw, Peng T., Limb, G. Astrid
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.03.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/2183; 631/378/2596; 631/378/2613/1786; 631/532; 631/80; Animals; ASCL1 protein; CD29 antigen; CD44 antigen; Cell Differentiation - genetics; Cell Proliferation; Developmental stages; Embryo cells; Embryogenesis; Ependymoglial Cells - metabolism; Gene expression; Glial stem cells; Homeostasis; Humanities and Social Sciences; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Mammals; Maturation; Mueller cells; multidisciplinary; Neuroglia - metabolism; Organoids; Pax6 protein; Quorum sensing; Retina; Retina - metabolism; Science; Science (multidisciplinary); Stem cells; Stem Cells - metabolism; Transcriptome; Transcriptomics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-32058-w

Müller glia play very important and diverse roles in retinal homeostasis and disease. Although much is known of the physiological and morphological properties of mammalian Müller glia, there is still the need to further understand the profile of these cells during human retinal development. Using human embryonic stem cell-derived retinal organoids, we investigated the transcriptomic profiles of CD29 + /CD44 + cells isolated from early and late stages of organoid development. Data showed that these cells express classic markers of retinal progenitors and Müller glia, including NFIX , RAX , PAX6 , VSX2 , HES1 , WNT2B , SOX , NR2F1 / 2 , ASCL1 and VIM , as early as days 10–20 after initiation of retinal differentiation. Expression of genes upregulated in CD29 + /CD44 + cells isolated at later stages of organoid development (days 50–90), including NEUROG1 , VSX2 and ASCL1 were gradually increased as retinal organoid maturation progressed. Based on the current observations that CD24 + /CD44 + cells share the characteristics of early and late-stage retinal progenitors as well as of mature Müller glia, we propose that these cells constitute a single cell population that upon exposure to developmental cues regulates its gene expression to adapt to functions exerted by Müller glia in the postnatal and mature retina.