A single‐cell transcriptome atlas of the adult human retina

• Published in: The EMBO journal Vol. 38; no. 18; pp. e100811 - n/a
• Main Authors: Lukowski, Samuel W, Lo, Camden Y, Sharov, Alexei A, Nguyen, Quan, Fang, Lyujie, Hung, Sandy SC, Zhu, Ling, Zhang, Ting, Grünert, Ulrike, Nguyen, Tu, Senabouth, Anne, Jabbari, Jafar S, Welby, Emily, Sowden, Jane C, Waugh, Hayley S, Mackey, Adrienne, Pollock, Graeme, Lamb, Trevor D, Wang, Peng‐Yuan, Hewitt, Alex W, Gillies, Mark C, Powell, Joseph E, Wong, Raymond CB
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.09.2019; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Amacrine cells; Astrocytes; Autopsy; Benchmarks; Biotechnology; Bipolar cells; Cluster Analysis; Clustering; Databases, Genetic; Degeneration; EMBO11; EMBO22; Functional morphology; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation; Gene sequencing; Horizontal cells; Human performance; Humans; Image processing; Microglia; Nerve Degeneration - genetics; Neuronal-glial interactions; Organ Specificity; Photoreception; photoreceptor subtypes; Photoreceptors; Pluripotency; Populations; Quality assessment; Resource; Resources; Retina; Retina - chemistry; Retinal cells; Retinal degeneration; Retinal ganglion cells; Retinal Rod Photoreceptor Cells - chemistry; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Sequence Analysis, RNA; Single-Cell Analysis - methods; single‐cell RNA sequencing; Stem cells; Transcription; Transcriptome; Unsupervised Machine Learning; retina; photoreceptor subtypes; transcriptome; single‐cell RNA sequencing; single-cell RNA sequencing
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.15252/embj.2018100811

The retina is a specialized neural tissue that senses light and initiates image processing. Although the functional organization of specific retina cells has been well studied, the molecular profile of many cell types remains unclear in humans. To comprehensively profile the human retina, we performed single‐cell RNA sequencing on 20,009 cells from three donors and compiled a reference transcriptome atlas. Using unsupervised clustering analysis, we identified 18 transcriptionally distinct cell populations representing all known neural retinal cells: rod photoreceptors, cone photoreceptors, Müller glia, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, astrocytes, and microglia. Our data captured molecular profiles for healthy and putative early degenerating rod photoreceptors, and revealed the loss of MALAT1 expression with longer post‐mortem time, which potentially suggested a novel role of MALAT1 in rod photoreceptor degeneration. We have demonstrated the use of this retina transcriptome atlas to benchmark pluripotent stem cell‐derived cone photoreceptors and an adult Müller glia cell line. This work provides an important reference with unprecedented insights into the transcriptional landscape of human retinal cells, which is fundamental to understanding retinal biology and disease. Synopsis The transcriptome of human neural retina at a single‐cell level defines the gene expression profile in major cell types in the neural retina and can be used as a benchmark to assess the quality of stem cell‐derived cells or primary retinal cells. The presented transcriptome atlas of human neural retina comprises single‐cell RNA‐sequencing data from 20,009 human retinal cells. Unsupervised cell clustering analysis allows identification of 18 transcriptionally distinct cell populations that represent all known neural retinal cell types. Reduced expression of the long non‐coding RNA MALAT1 correlates with longer post‐mortem time in putative early degenerating rod photoreceptors. The retina transcriptome atlas can be used to benchmark pluripotent stem cell‐derived cone photoreceptors and an adult Müller glia cell line. Graphical Abstract A comprehensive analysis of the human retinal transcriptome at a single‐cell level defines gene expression profiles of all major retinal cell types.