» Articles » PMID: 29233477

Molecular Anatomy of the Developing Human Retina

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.

Citing Articles

Spatiotemporally resolved transcriptomics reveals the cellular dynamics of human retinal development.

Zhang J, Wang J, Zhou Q, Chen Z, Zhuang J, Zhao X Nat Commun. 2025; 16(1):2307.

PMID: 40055379 PMC: 11889126. DOI: 10.1038/s41467-025-57625-9.


Differentiation versus dysfunction: thyroid hormone, deiodinases and retinal photoreceptors.

Ng L, Liu Y, Cho Y, Liu H, Forrest D Eur Thyroid J. 2025; 14(2).

PMID: 40019772 PMC: 11906153. DOI: 10.1530/ETJ-24-0315.


Derivation and Characterization of Isogenic Mutant and Control Human Pluripotent Stem Cell Lines.

Pohl K, Zhang X, Ji J, Stiles L, Sadun A, Yang X Cells. 2025; 14(2).

PMID: 39851566 PMC: 11764107. DOI: 10.3390/cells14020137.


Unraveling the developmental heterogeneity within the human retina to reconstruct the continuity of retinal ganglion cell maturation and stage-specific intrinsic and extrinsic factors.

Kriukov E, Soucy J, Labrecque E, Baranov P bioRxiv. 2024; .

PMID: 39464118 PMC: 11507843. DOI: 10.1101/2024.10.16.618776.


Retinal ganglion cell circuits and glial interactions in humans and mice.

Huang K, Tawfik M, Samuel M Trends Neurosci. 2024; 47(12):994-1013.

PMID: 39455342 PMC: 11631666. DOI: 10.1016/j.tins.2024.09.010.


References
1.
Veleri S, Nellissery J, Mishra B, Manjunath S, Brooks M, Dong L . REEP6 mediates trafficking of a subset of Clathrin-coated vesicles and is critical for rod photoreceptor function and survival. Hum Mol Genet. 2017; 26(12):2218-2230. PMC: 5458339. DOI: 10.1093/hmg/ddx111. View

2.
Kozulin P, Natoli R, OBrien K, Madigan M, Provis J . Differential expression of anti-angiogenic factors and guidance genes in the developing macula. Mol Vis. 2009; 15:45-59. PMC: 2622716. View

3.
Hornan D, Peirson S, Hardcastle A, Molday R, Cheetham M, Webster A . Novel retinal and cone photoreceptor transcripts revealed by human macular expression profiling. Invest Ophthalmol Vis Sci. 2007; 48(12):5388-96. DOI: 10.1167/iovs.07-0355. View

4.
Llamosas M, Cernuda-Cernuda R, Huerta J, Vega J, Garcia-Fernandez J . Neurotrophin receptors expression in the developing mouse retina: an immunohistochemical study. Anat Embryol (Berl). 1997; 195(4):337-44. DOI: 10.1007/s004290050053. View

5.
La Torre A, Georgi S, Reh T . Conserved microRNA pathway regulates developmental timing of retinal neurogenesis. Proc Natl Acad Sci U S A. 2013; 110(26):E2362-70. PMC: 3696811. DOI: 10.1073/pnas.1301837110. View