Longitudinal single-cell RNA-seq of hESCs-derived retinal organoids

Sci China Life Sci. 2021 Oct;64(10):1661-1676. doi: 10.1007/s11427-020-1836-7. Epub 2021 Jan 27.

Abstract

Human retina development involves multiple well-studied signaling pathways that promote the genesis of a wide arrange of different cell types in a complex architectural structure. Human embryonic stem cells (hESCs)-derived retinal organoids could recapitulate the human retinal development. We performed single-cell RNA-seq of retinal organoids from 5 time points (D36, D66, D96, D126, D186) and identified 9 distinct populations of cells. In addition, we analyzed the molecular characteristics of each main population and followed them from genesis to maturity by pseudotime analysis and characterized the cell-cell interactions between different cell types. Interestingly, we identified insulin receptor (INSR) as a specifically expressed receptor involved in the genesis of photoreceptors, and pleiothropin (PTN)-protein tyrosine phosphatase receptor type Z1 (PTPRZ1) as a mediator of a previously unknown interaction between Müller and retinal progenitor cells. Taken together, these findings provide a rich transcriptome-based lineage map for studying human retinal development and modeling developmental disorders in retinal organoids.

Keywords: human embryonic stem cell; photoreceptor cell; retinal organoid; retinal pigment epithelium; single cell RNA sequencing.

MeSH terms

  • Cell Communication
  • Cell Lineage
  • Gene Expression Profiling
  • Human Embryonic Stem Cells / cytology
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Organoids / cytology
  • Organoids / growth & development
  • Organoids / metabolism*
  • Photoreceptor Cells, Vertebrate / metabolism
  • RNA-Seq
  • Receptor, Insulin / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
  • Retina / cytology
  • Retina / growth & development
  • Retina / metabolism*
  • Retinal Ganglion Cells / metabolism
  • Retinal Pigment Epithelium / metabolism
  • Single-Cell Analysis
  • Stem Cells / metabolism

Substances

  • Receptor, Insulin
  • PTPRZ1 protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5