Mar 3, 2020

Combined analysis of single cell RNA-Seq and ATAC-Seq data reveals regulatory toggles operating in native and iPS-derived retina.

bioRxiv
Anouk GeorgesMichel Georges

Abstract

We herein report the generation and analysis of single-cell RNA Seq data (> 38,000 cells) from native and iPSC-derived murine retina at four matched developmental stages spanning the emergence of the major retinal cell types. We combine information from temporal sampling, visualization of 3D UMAP manifolds in virtual reality, and RNA velocity analysis to show that iPSC-derived 3D retinal aggregates broadly recapitulate the native developmental trajectories with evidence supporting re-specification from amacrine cells to horizontal and photoreceptor precursor cells, as well as a direct differentiation of Tbr1+ retinal ganglion cells from neuro-epithelium cells. We show 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 iPSC-derived retina. We generate bulk ATAC-Seq data for native and iPSC-derived murine retina at three of the four same developmental stages identifying ~125,000 peaks. The number of ATAC-Seq peaks increased with developmental stage in native but not in iPSC-derived retina. We combine single-cell RNA Seq with ATAC-Seq information and demo...Continue Reading

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Mentioned in this Paper

Fibroblast-Derived Induced Pluripotent Stem Cells
Disease Susceptibility
Horizontal
Three-dimensional
Retina
Retinal Development
Transcriptome
Regulation of Signaling Pathway
Cell Differentiation Process
Repressor Proteins

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