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Dev Cell. 2017 Dec 18;43(6):763-779.e4. doi: 10.1016/j.devcel.2017.10.029. Epub 2017 Dec 7.

Molecular Anatomy of the Developing Human Retina.

Author information

1
Department of Biological Structure, University of Washington, Seattle, WA 98105, USA.
2
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
3
Department of Biological Structure, University of Washington, Seattle, WA 98105, USA; Department of Cell Biology and Human Anatomy, University of California Davis, Davis, CA 95616, USA.
4
Department of Pediatrics and Medicine, University of Washington School of Medicine, Seattle, WA 98105, USA.
5
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: swaroopa@nei.nih.gov.
6
Department of Biological Structure, University of Washington, Seattle, WA 98105, USA. Electronic address: tomreh@uw.edu.

Abstract

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.

KEYWORDS:

development; fetal; fovea; gene network; human; macula; organoids; photoreceptor; retina; transcriptome

PMID:
29233477
PMCID:
PMC5776731
[Available on 2018-12-18]
DOI:
10.1016/j.devcel.2017.10.029
[Indexed for MEDLINE]

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