@article{2506, author = {Philipp Wahle and Giovanna Brancati and Christoph Harmel and Zhisong He and Gabriele Gut and Jacobo Sarabia Del Castillo and Aline Xavier da Silveira Dos Santos and Qianhui Yu and Pascal Noser and Jonas Simon Fleck and Bruno Gjeta and Dinko Pavlinic and Simone Picelli and Max Hess and Gregor W. Schmidt and Tom T. A. Lummen and Yanyan Hou and Patricia Galliker and David Goldblum and Marton Balogh and Cameron S. Cowan and Hendrik P. N. Scholl and Botond Roska and Magdalena Renner and Lucas Pelkmans and Barbara Treutlein and J. Gray Camp}, title = {Multimodal spatiotemporal phenotyping of human retinal organoid development}, 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.}, year = {2023}, journal = {Nature Biotechnology}, month = {2023-05-08}, issn = {1546-1696}, doi = {10.1038/s41587-023-01747-2}, language = {eng}, }