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Cell. 2019 Feb 21;176(5):1222-1237.e22. doi: 10.1016/j.cell.2019.01.004. Epub 2019 Jan 31.

Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina.

Author information

1
Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
2
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
3
F.M. Kirby Neurobiology Center and Department of Neurology, Boston Children's Hospital Harvard Medical School, Boston, MA 02115, USA.
4
Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
5
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA.
6
Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: sanesj@mcb.harvard.edu.

Abstract

High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.

PMID:
30712875
DOI:
10.1016/j.cell.2019.01.004

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