A single-cell transcriptome atlas of the adult human retina

Samuel W. Lukowski, Camden Y. Lo, Alexei A. Sharov, Quan Nguyen, Lyujie Fang, Sandy S.C. Hung, Ling Zhu, Ting Zhang, Ulrike Grünert, Tu Nguyen, Anne Senabouth, Jafar S. Jabbari, Emily Welby, Jane C. Sowden, Hayley S. Waugh, Adrienne Mackey, Graeme Pollock, Trevor D. Lamb, Peng Yuan Wang, Alex W. HewittMark C. Gillies, Joseph E. Powell, Raymond C.B. Wong*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    159 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Article numbere100811
    JournalEMBO Journal
    Volume38
    Issue number18
    DOIs
    Publication statusPublished - 16 Sept 2019

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