Comparing the transcriptome of developing native and iPSC-derived mouse retinae by single cell RNA sequencing

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Genomics

Background:

• Induced pluripotent stem cells (iPSCs) offer a promising model for studying human retinal development and diseases.
• Understanding the precise developmental trajectories in vitro is crucial for accurate disease modeling and therapeutic development.

Purpose of the Study:

• To compare the developmental trajectories of mouse native retinae and iPSC-derived retinal organoids using single-cell RNA sequencing.
• To identify discrepancies and conserved features in retinal development between native tissues and organoids.
• To assess the utility of retinal organoids for modeling retinopathies by analyzing disease-associated genes.

Main Methods:

• Generation and analysis of single-cell RNA-Seq data from over 38,000 cells from mouse native retinae and iPSC-derived retinal organoids.
• Utilized temporal sampling, 3D UMAP visualization, pseudo-time, and RNA velocity analyses to track developmental trajectories.
• Investigated the enrichment and conservation of genes associated with human retinopathies.

Main Results:

• iPSC-derived retinal organoids broadly recapitulate native retinal developmental trajectories.
• Observed relaxation of spatial and temporal transcriptome control, and premature photoreceptor precursor cell emergence in organoids.
• Identified conserved expression profiles for a subset of human retinopathies-causing genes between human retinae and murine organoids.

Conclusions:

• While iPSC-derived retinal organoids are valuable models, they exhibit altered gene regulation compared to native retinae.
• Retinal organoids can be used to study conserved disease mechanisms in retinopathies.
• This study provides a valuable resource for improving retinal organoid protocols and disease modeling.