Molecular Anatomy of the Developing Human Retina

• DOI: 10.1016/j.devcel.2017.10.029
• Publication Date: 2017-12-07T12:42:29Z
• Authors: Akina Hoshino; Rinki Ratnapriya; Matthew J. Brooks; Vijender Chaitankar; Matthew S. Wilken; Chi Zhang; Margaret R. Staro...; Linn Gieser; Anna La Torre; Mario Nishio; Olivia Bates; Ashley Walton; Olivia Bermingham...; Ian A. Glass; Rachel O.L. Wong; Anand Swaroop; Thomas A. Reh
• Keywords: Neurons; 0301 basic medicine; Fovea Centralis; Sequence Analysis, RNA; Neurogenesis; Gene Expression Regulation, Developmental; Retina; 3. Good health; Mice; 03 medical and health sciences; Morphogenesis; Animals; Humans; Gene Regulatory Networks; Macula Lutea; Eye Proteins; Transcriptome

Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, although morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as a resource for molecular staging of human stem-cell-derived retinal organoids.