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

We report the generation and analysis of single-cell RNA-Seq data (> 38,000 cells) from mouse native retinae and induced pluripotent stem cell (iPSC)-derived retinal organoids at four matched stages of development spanning the emergence of the major retinal cell types. We combine information from...

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Bibliographic Details
Published in:Scientific reports 2023-01, Vol.13 (1), p.1223-1223, Article 1223
Main Authors: Georges, Anouk, Lavergne, Arnaud, Mandai, Michiko, Lepiemme, Fanny, Karim, Latifa, Demeulenaere, Loic, Aguilar, Diego, Schyns, Michael, Nguyen, Laurent, Rakic, Jean-Marie, Takahashi, Masayo, Georges, Michel, Takeda, Haruko
Format: Article
Language:English
Subjects:
631/136
631/532
Animals
Cell culture
Cell cycle
Cell Differentiation
Cell Differentiation - genetics
Developmental stages
Gene expression
Genetics & genetic processes
Genomics
Génétique & processus génétiques
Humanities and Social Sciences
Humans
Induced Pluripotent Stem Cells
Life sciences
Mice
Multidisciplinary
Organoids
Organoids - metabolism
Photoreceptor Cells
Photoreceptors
Pluripotency
Retina
Retina - metabolism
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Sciences du vivant
Sequence Analysis, RNA
Stem cells
Transcription factors
Transcriptome
Transcriptomes
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Summary:We report the generation and analysis of single-cell RNA-Seq data (> 38,000 cells) from mouse native retinae and induced pluripotent stem cell (iPSC)-derived retinal organoids at four matched stages of development spanning the emergence of the major retinal cell types. We combine information from temporal sampling, visualization of 3D UMAP manifolds, pseudo-time and RNA velocity analyses, to show that iPSC-derived 3D retinal organoids broadly recapitulate the native developmental trajectories. However, we observe relaxation of spatial and temporal transcriptome control, premature emergence and dominance of photoreceptor precursor cells, and susceptibility of dynamically regulated pathways and transcription factors to culture conditions in retinal organoids. We demonstrate that genes causing human retinopathies are enriched in cell-type specifying genes and identify a subset of disease-causing genes with expression profiles that are highly conserved between human retinae and murine retinal organoids. This study provides a resource to the community that will be useful to assess and further improve protocols for ex vivo recapitulation and study of retinal development.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-28429-y