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Retina is a crucial tissue for capturing and processing light stimulus. It is critical to describe the characteristics of retina at the single-cell level for understanding its biological functions. A variety of abnormalities in terms of morphology and function are present in the trisomy 21 (T21) retina. To evaluate the consequences of chromosome aneuploidy on retina development, we identified the single-cell transcriptional profiles of a T21 fetus and performed comprehensive bioinformatic analyses. Our data revealed the diversity and heterogeneity of cellular compositions in T21 retina, as well as the abnormal constitution of T21 retina compared to disomic retina. In total, we identified seven major cell types and several subtypes within each cell type, followed by the detection of corresponding molecular markers, including previously reported ones and a series of novel markers. Through the analysis of the retinal differentiation process, subtypes of retinal progenitor cells (RPCs) exhibiting the potential of different retinal cell-type commitments and certain Müller glial cells (MGs) with differentiating potency were identified. Moreover, the extensive communication networks between cellular types were confirmed, among which a few ligand–receptor interactions were related to the formation and function of retina and immunoregulatory interactions. Taken together, our data provides the first ever single-cell transcriptome profiles for human T21 retina, which facilitates the understanding on the dosage effects of chromosome 21 on the development of retina.

Cell Development Deficiency and Gene Expression Dysregulation of Trisomy 21 Retina Revealed by Single-Nucleus RNA Sequencing