02178nas a2200433   4500000000100000000000100001008004100002260001500043100001800058700002200076700002100098700001500119700001700134700003200151700004000183700001500223700001700238700002200255700001600277700001900293700001900312700001300331700002200344700002100366700001500387700002200402700001900424700001800443700002100461700002500482700001700507700002100524700001900545700002200564700001700586245008000603520104700683022001401730       2023                            d  c2023-05-081 aPhilipp Wahle1 aGiovanna Brancati1 aChristoph Harmel1 aZhisong He1 aGabriele Gut1 aJacobo Sarabia Del Castillo1 aAline Xavier da Silveira Dos Santos1 aQianhui Yu1 aPascal Noser1 aJonas Simon Fleck1 aBruno Gjeta1 aDinko Pavlinic1 aSimone Picelli1 aMax Hess1 aGregor W. Schmidt1 aTom T. A. Lummen1 aYanyan Hou1 aPatricia Galliker1 aDavid Goldblum1 aMarton Balogh1 aCameron S. Cowan1 aHendrik P. N. Scholl1 aBotond Roska1 aMagdalena Renner1 aLucas Pelkmans1 aBarbara Treutlein1 aJ. Gray Camp00aMultimodal spatiotemporal phenotyping of human retinal organoid development3 aOrganoids 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.  a1546-1696