Article (Scientific journals)
Comparing the transcriptome of developing native and iPSC-derived mouse retinae by single cell RNA sequencing.
Georges, Anouk; Lavergne, Arnaud; Mandai, Michiko et al.
2023In Scientific Reports, 13 (1), p. 1223
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Keywords :
Mice; Humans; Animals; Transcriptome; Retina/metabolism; Photoreceptor Cells; Organoids/metabolism; Sequence Analysis, RNA; Cell Differentiation/genetics; Induced Pluripotent Stem Cells; Cell Differentiation; Organoids; Retina; Multidisciplinary
Abstract :
[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Georges, Anouk ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'ophtalmologie
Lavergne, Arnaud  ;  Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale
Mandai, Michiko;  Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe, Japan
Lepiemme, Fanny ;  Université de Liège - ULiège > GIGA
Karim, Latifa ;  Université de Liège - ULiège > GIGA > GIGA Platform Genomics
Demeulenaere, Loïc  ;  Université de Liège - ULiège > GIGA > GIGA Medical Genomics - Unit of Animal Genomics
Aguilar Ortmans, Diego ;  Université de Liège - ULiège > GIGA > GIGA I3 - Immunology & Infectious Diseases
Schyns, Michael ;  Université de Liège - ULiège > HEC Liège : UER > UER Opérations : Informatique de gestion
Nguyen, Laurent  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Rakic, Jean-Marie ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'ophtalmologie
Takahashi, Masayo;  Laboratory for Retinal Regeneration, Center for Biosystems Dynamics Research, RIKEN, Kobe, Japan
Georges, Michel  ;  Université de Liège - ULiège > GIGA > GIGA Innovation
Takeda, Haruko ;  Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale
More authors (3 more) Less
Language :
English
Title :
Comparing the transcriptome of developing native and iPSC-derived mouse retinae by single cell RNA sequencing.
Publication date :
21 January 2023
Journal title :
Scientific Reports
eISSN :
2045-2322
Publisher :
Nature Research, England
Volume :
13
Issue :
1
Pages :
1223
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
We are grateful to Tomoyo Hashiguchi for teaching the retinal organoid culture protocol and to Tomohiro Masuda and Akishi Onishi for their comments and suggestions. We thank the GIGA Genomics platform for their help both with scRNA-Seq experiments and early bio-informatic analyses (especially Wouter Coppieters and Benoit Charloteaux). We are grateful to Vincent Lambert for assisting with dissection of NaR. This work was financially supported by the “King Baudouin Foundation”, the “Global Ophthalmology Awards Program (GOAP) from Bayer”, and the “Fonds Leon Fredericq”. L.D. and L.N. are respectively postdoctoral researcher and senior associate researcher of the FRS-FNRS.
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