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- Title
Investigating cone photoreceptor development using patient-derived NRL null retinal organoids.
- Authors
Kallman, Alyssa; Capowski, Elizabeth E.; Wang, Jie; Kaushik, Aniruddha M.; Jansen, Alex D.; Edwards, Kimberly L.; Chen, Liben; Berlinicke, Cynthia A.; Joseph Phillips, M.; Pierce, Eric A.; Qian, Jiang; Wang, Tza-Huei; Gamm, David M.; Zack, Donald J.
- Abstract
Photoreceptor loss is a leading cause of blindness, but mechanisms underlying photoreceptor degeneration are not well understood. Treatment strategies would benefit from improved understanding of gene-expression patterns directing photoreceptor development, as many genes are implicated in both development and degeneration. Neural retina leucine zipper (NRL) is critical for rod photoreceptor genesis and degeneration, with NRL mutations known to cause enhanced S-cone syndrome and retinitis pigmentosa. While murine Nrl loss has been characterized, studies of human NRL can identify important insights for human retinal development and disease. We utilized iPSC organoid models of retinal development to molecularly define developmental alterations in a human model of NRL loss. Consistent with the function of NRL in rod fate specification, human retinal organoids lacking NRL develop S-opsin dominant photoreceptor populations. We report generation of two distinct S-opsin expressing populations in NRL null retinal organoids and identify MEF2C as a candidate regulator of cone development. Kallman et al. showed the effect of Nrl in human PSC-derived retinal organoids. Using histological and single cell transcriptomics, they identified an intermediate "cod" subpopulation in the predominant S-opsin population. Their findings provide important insights for human retinal development and degeneration.
- Subjects
PHOTORECEPTORS; ORGANOIDS; BLINDNESS; GENE expression; RETINAL development
- Publication
Communications Biology, 2020, Vol 3, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-020-0808-5