학술논문
Multimodal spatiotemporal phenotyping of human retinal organoid development
Document Type
Original Paper
Author
Wahle, Philipp; Brancati, Giovanna; Harmel, Christoph; He, Zhisong; Gut, Gabriele; del Castillo, Jacobo Sarabia; Xavier da Silveira dos Santos, Aline; Yu, Qianhui; Noser, Pascal; Fleck, Jonas Simon; Gjeta, Bruno; Pavlinić, Dinko; Picelli, Simone; Hess, Max; Schmidt, Gregor W.; Lummen, Tom T. A.; Hou, Yanyan; Galliker, Patricia; Goldblum, David; Balogh, Marton; Cowan, Cameron S.; Scholl, Hendrik P. N.; Roska, Botond; Renner, Magdalena; Pelkmans, Lucas; Treutlein, Barbara; Camp, J. Gray
Source
Nature Biotechnology: The Science and Business of Biotechnology. 41(12):1765-1775
Subject
Language
English
ISSN
1087-0156
1546-1696
1546-1696
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.
A multimodal atlas of retinal organoid development shows spatial interactions over time.
A multimodal atlas of retinal organoid development shows spatial interactions over time.