Dissecting the transcriptome landscape of the human fetal neural retina and retinal pigment epithelium by single-cell RNA-seq analysis

PLoS Biol. 2019 Jul 3;17(7):e3000365. doi: 10.1371/journal.pbio.3000365. eCollection 2019 Jul.

Abstract

The developmental pathway of the neural retina (NR) and retinal pigment epithelium (RPE) has been revealed by extensive research in mice. However, the molecular mechanisms underlying the development of the human NR and RPE, as well as the interactions between these two tissues, have not been well defined. Here, we analyzed 2,421 individual cells from human fetal NR and RPE using single-cell RNA sequencing (RNA-seq) technique and revealed the tightly regulated spatiotemporal gene expression network of human retinal cells. We identified major cell classes of human fetal retina and potential crucial transcription factors for each cell class. We dissected the dynamic expression patterns of visual cycle- and ligand-receptor interaction-related genes in the RPE and NR. Moreover, we provided a map of disease-related genes for human fetal retinal cells and highlighted the importance of retinal progenitor cells as potential targets of inherited retinal diseases. Our findings captured the key in vivo features of the development of the human NR and RPE and offered insightful clues for further functional studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Cycle / genetics
  • Cells, Cultured
  • Cluster Analysis
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Developmental*
  • Gene Ontology
  • Humans
  • Retina / cytology
  • Retina / embryology
  • Retina / metabolism*
  • Retinal Diseases / genetics
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / embryology
  • Retinal Pigment Epithelium / metabolism*
  • Sequence Analysis, RNA / methods*
  • Single-Cell Analysis / methods*
  • Transcriptome*

Grants and funding

JQ and FT were supported by grants from the National Basic Research Program of China (2018YFA0107601) and the National Natural Science Foundation of China (31625018, 31522034, 31571544, and 81521002); YH was supported in part by the Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.