BEL contribution to article on retina organoids in "Cell"
BEL contributed large-scale electrophysiological measurements and corresponding data analysis to characterization of light-sensitive human retinal organoids, developed by Roska group at IOB. Results have been published in journal Cell.
Human organoids are 3D cellular ensembles that are grown in vitro from adult or pluripotent stem cells and reproduce some morphological, functional, and transcriptomic features of human organs. Organoids engineered to harbor disease-causing mutations or grown directly from patient cells could provide mechanistic insights into diseases.
The Roska group at IOB developed retinal organoids with three nuclear and two synaptic layers from human induced pluripotent stem cells (iPSCs) and produced those in large quantities. The photoreceptors of the organoids responded to light and transmitted visual information synaptically, generating light responses in second- or third-order retinal cells. They showed that adult human retinal cell type transcriptomes change rapidly post mortem in ischemia and developed a procedure to obtain adult human retinas that were exposed to less than 5 min of ischemia and maintained light responses and functional retinal circuits for 16 h ex vivo. By comparing organoids to organs, they could show that transcriptomes of organoid cell types converged to those of adult human peripheral retinas. They also compared developed organoids and adult human retinas in their expression of genes associated with retinal diseases. The resulting genetic disease maps showed retinal diseases to be cell-type-specific and that cell-type specificity is preserved in organoids. The results were reported in an article in the journal Cell: C. S. Cowan, M. Renner, et al., "Cell types of the human retina and its organoids at single-cell resolution", Cell 2020, Vol. 182(6), pp. 1623-1640.e34 (DOI: 10.1016/j.cell.2020.08.013).
BEL and, specifically, R. Diggelmann, who is a co-author, contributed large-scale electrophysiological measurements by means of high-density microelectrode arrays and the corresponding data analysis to characterize light-sensitive human retinal organoids and retinae.
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