Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types

Tavé van Zyl, Wenjun Yan, Alexi M. McAdams, Aboozar Monavarfeshani, Gregory S. Hageman, Joshua R. Sanes

Abstract

The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens, and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some disorders, including glaucoma and cataract, are among the most prevalent causes of blindness in the world. To characterize the cell types that compose these tissues, we generated an anterior segment cell atlas of the human eye using high-throughput single-nucleus RNA sequencing (snRNAseq). We profiled 195,248 nuclei from nondiseased anterior segment tissues of six human donors, identifying >60 cell types. Many of these cell types were discrete, whereas others, especially in the lens and cornea, formed continua corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment, revealing that some cell types are unique to a single structure, whereas others are shared across tissues. The integrated cell atlas was then used to investigate cell type–specific expression patterns of more than 900 human ocular disease genes identified through either Mendelian inheritance patterns or genome-wide association studies.

Datasets

1. Iris
Metadata
donor_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sample_uuid
sample_preservation_method
tissue_ontology_term_id
development_stage_ontology_term_id
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library_uuid
assay_ontology_term_id
mapped_reference_annotation
cell_type_ontology_term_id
author_cell_type
disease_ontology_term_id
sex_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
sanes2022_Hu023514672 cells
pooled [sanes2022_Hu0220,sanes2022_Hu0235]13664 cells
pooled [sanes2022_Hu0216,sanes2022_Hu0218]11917 cells
sanes2022_Hu02167898 cells
sanes2022_Hu02206821 cells
sanes2022_Hu02182450 cells
Preview
Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types
2. Trabecular Meshwork and Corneal Scleral wedge
Metadata
donor_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sample_uuid
sample_preservation_method
tissue_ontology_term_id
development_stage_ontology_term_id
suspension_uuid
suspension_type
library_uuid
assay_ontology_term_id
mapped_reference_annotation
cell_type_ontology_term_id
author_cell_type
disease_ontology_term_id
sex_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
sanes2022_Hu022018617 cells
sanes2022_Hu021616580 cells
sanes2022_Hu021811037 cells
sanes2022_Hu02356075 cells
Preview
Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types
3. Central Cornea
Metadata
donor_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sample_uuid
sample_preservation_method
tissue_ontology_term_id
development_stage_ontology_term_id
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library_uuid
assay_ontology_term_id
mapped_reference_annotation
cell_type_ontology_term_id
author_cell_type
disease_ontology_term_id
sex_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
sanes2022_Hu021611820 cells
sanes2022_Hu02208461 cells
sanes2022_Pt146150 cells
sanes2022_Hu02186045 cells
sanes2022_Hu02355009 cells
Preview
Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types
4. Ciliary Body
Metadata
donor_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sample_uuid
sample_preservation_method
tissue_ontology_term_id
development_stage_ontology_term_id
suspension_uuid
suspension_type
library_uuid
assay_ontology_term_id
mapped_reference_annotation
cell_type_ontology_term_id
author_cell_type
disease_ontology_term_id
reported_diseases
sex_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
sanes_Pt210340 cells
sanes2022_Hu02208420 cells
sanes2022_Hu02357949 cells
sanes2022_Hu02167423 cells
Preview
Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types
5. Lens
Metadata
donor_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sample_uuid
sample_preservation_method
tissue_ontology_term_id
development_stage_ontology_term_id
suspension_uuid
suspension_type
library_uuid
assay_ontology_term_id
mapped_reference_annotation
cell_type_ontology_term_id
author_cell_type
disease_ontology_term_id
sex_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
pooled [sanes2022_Hu0216,sanes2022_Hu0235]5963 cells
pooled [sanes2022_Hu0220,sanes2022_Hu0218]5334 cells
sanes2022_Pt142603 cells
Preview
Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types

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Source data

https://cellxgene.cziscience.com/collections/63d03351-06be-478e-a0db-f7a653b6b19b

Alias names

GSE199013, SCP1841, PMID35858321, PMC9303934

Cite this study

van Zyl, T., Yan, W., McAdams, A.M., Monavarfeshani, A., Hageman, G.S. and Sanes, J.R., 2022. Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types. Proceedings of the National Academy of Sciences, 119(29), p.e2200914119. https://doi.org/10.1073/pnas.2200914119