Single-cell transcriptomic atlas of human retina from Chinese donors reveals population-specific cellular diversity

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Abstract
The human retina exhibits complex cellular heterogeneity which is critical for visual function, yet comprehensive ethnic-specific references are scarce in ophthalmic transcriptomics. The lack of single-cell RNA sequencing (scRNA-seq) data from Asian populations particularly Chinese donors imposes significant limitations in understanding population-specific retinal biology. We constructed the first comprehensive single-cell transcriptomic atlas of the human retina from Chinese donors, generated through high-throughput scRNA-seq of ∼290,000 viable cells obtained from 18 fresh retinal specimens (living donor and post-mortem specimens). Our multi-level analysis identified 10 distinct retinal cell types, encompassing all major neuronal lineages, Müller glia, astrocytes, microglia. Detailed subcluster analyses further revealed extensive heterogeneity, identifying distinct subtypes within several cell populations such as 7 amacrine cell subtypes and 14 bipolar cell subtypes. Concurrently, through systematic analysis of delineated subtype-specific molecular programs, we mapped their associated biological signaling pathways, functions, and mechanistic processes. This analysis explained the critical involvement of these subpopulations in core biological processes including synaptic organization, neurotransmission, and phototransduction cascades, potentially governing retinal homeostatic regulation and disease mechanisms. Single-cell transcriptomic atlas of the human retina from Chinese donors describes a comprehensive cellular landscape, encompassing major cell types and subtypes including neuronal, glial, and immune populations. This ethnic-specific atlas provided an important reference for understanding retinal development, cellular interaction and disease pathogenesis in Chinese populations, addressing a longstanding gap in ophthalmic transcriptomic resources.
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