TY - JOUR
AU - Philipp Wahle
AU - Giovanna Brancati
AU - Christoph Harmel
AU - Zhisong He
AU - Gabriele Gut
AU - Jacobo Sarabia Del Castillo
AU - Aline Xavier da Silveira Dos Santos
AU - Qianhui Yu
AU - Pascal Noser
AU - Jonas Simon Fleck
AU - Bruno Gjeta
AU - Dinko Pavlinic
AU - Simone Picelli
AU - Max Hess
AU - Gregor W. Schmidt
AU - Tom T. A. Lummen
AU - Yanyan Hou
AU - Patricia Galliker
AU - David Goldblum
AU - Marton Balogh
AU - Cameron S. Cowan
AU - Hendrik P. N. Scholl
AU - Botond Roska
AU - Magdalena Renner
AU - Lucas Pelkmans
AU - Barbara Treutlein
AU - J. Gray Camp
AB - 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.
BT - Nature Biotechnology
DA - 2023-05-08
DO - 10.1038/s41587-023-01747-2
LA - eng
N2 - 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.
PY - 2023
T2 - Nature Biotechnology
TI - Multimodal spatiotemporal phenotyping of human retinal organoid development
SN - 1546-1696
ER -