title: Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early developmental stages of human retinal ganglion cells in embryonic stem cell derived retina.
abstract: Human retinal ganglion cells (RGCs) derived from pluripotent stem cells (PSCs) have anticipated value for human disease study, drug screening, and therapeutic applications; however, their full potential remains underdeveloped. To characterize RGCs in human embryonic stem cell (hESC) derived retinal organoids we examined RGC markers and surface antigen expression and made comparisons to human fetal retina. RGCs in both tissues exhibited CD184 and CD171 expression and distinct expression patterns of the RGC markers BRN3 and RBPMS. The retinal progenitor cells (RPCs) of retinal organoids expressed CD184, consistent with its expression in the neuroblastic layer in fetal retina. In retinal organoids CD184 expression was enhanced in RGC competent RPCs and high CD184 expression was retained on post-mitotic RGC precursors; CD171 was detected on maturing RGCs. The differential expression timing of CD184 and CD171 permits identification and enrichment of RGCs from retinal organoids at differing maturation states from committed progenitors to differentiating neurons. These observations will facilitate molecular characterization of PSC-derived RGCs during differentiation, critical knowledge for establishing the veracity of these in vitro produced cells. Furthermore, observations made in the retinal organoid model closely parallel those in human fetal retina further validating use of retinal organoid to model early retinal development.
authors.affiliation: The Vision Center, Division of Ophthalmology, and Department of Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA. Electronic address: japaricio@chla.usc.edu.
authors.forename: J G
authors.initials: JG
authors.lastname: Aparicio
authors.affiliation: The Vision Center, Division of Ophthalmology, and Department of Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hopp
authors.affiliation: The Vision Center, Division of Ophthalmology, and Department of Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Choi
authors.affiliation: California Institute of Technology, Pasadena, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mandayam Comar
authors.affiliation: The Vision Center, Division of Ophthalmology, and Department of Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: V C
authors.initials: VC
authors.lastname: Liao
authors.affiliation: The Vision Center, Division of Ophthalmology, and Department of Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Harutyunyan
authors.affiliation: The Vision Center, Division of Ophthalmology, and Department of Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Ophthalmology and USC Eye Institute, University of Southern California, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis / Q000235:genetics*; D009940:Organoids / Q000196:embryology / Q000378:metabolism; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics*; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C527276:CXCR4 protein, human; D039842:Neural Cell Adhesion Molecule L1; D019718:Receptors, CXCR4; D012313:RNA
keywords: CD171 (L1CAM); CD184(CXCR4); RBPMS; Retina development; Retinal ganglion cell; Retinal organoid; Stem cell derived retina