Multimodal spatiotemporal phenotyping of human retinal organoid development

Philipp Wahle, Giovanna Brancati, Christoph Harmel, Zhisong He, Gabriele Gut, Jacobo Sarabia del Castillo, Aline Xavier da Silveira dos Santos, Qianhui Yu, Pascal Noser, Jonas Simon Fleck, Bruno Gjeta, Dinko Pavlinić, Simone Picelli, Max Hess, Gregor W. Schmidt, Tom T.A. Lummen, Yanyan Hou, Patricia Galliker, David Goldblum, Marton BaloghCameron S. Cowan, Hendrik P.N. Scholl, Botond Roska, Magdalena Renner, Lucas Pelkmans, Barbara Treutlein, J. Gray Camp

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Organoids generated from human pluripotent stem cells provide experimental systems to study development and disease, but quantitative measurements across different spatial scales and molecular modalities are lacking. In this study, we generated multiplexed protein maps over a retinal organoid time course and primary adult human retinal tissue. We developed a toolkit to visualize progenitor and neuron location, the spatial arrangements of extracellular and subcellular components and global patterning in each organoid and primary tissue. In addition, we generated a single-cell transcriptome and chromatin accessibility timecourse dataset and inferred a gene regulatory network underlying organoid development. We integrated genomic data with spatially segmented nuclei into a multimodal atlas to explore organoid patterning and retinal ganglion cell (RGC) spatial neighborhoods, highlighting pathways involved in RGC cell death and showing that mosaic genetic perturbations in retinal organoids provide insight into cell fate regulation.

Original languageEnglish
Pages (from-to)1765-1775
Number of pages11
JournalNature Biotechnology
Volume41
Issue number12
DOIs
StatePublished - Dec 2023
Externally publishedYes

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