A Single-Cell Transcriptome Atlas of the Adult Human Retina

EMBO J. 2019 Sep 16;38(18):e100811. doi: 10.15252/embj.2018100811. Epub 2019 Aug 22.

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.

Keywords: photoreceptor subtypes; retina; single-cell RNA sequencing; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autopsy
  • Cluster Analysis
  • Databases, Genetic
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Humans
  • Nerve Degeneration / genetics*
  • Organ Specificity
  • RNA, Long Noncoding / genetics*
  • Retina / chemistry*
  • Retinal Rod Photoreceptor Cells / chemistry
  • Sequence Analysis, RNA
  • Single-Cell Analysis / methods*
  • Transcriptome*
  • Unsupervised Machine Learning

Substances

  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding