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Spatiotemporal, optogenetic control of gene expression in organoids

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Item Type:Article
Title:Spatiotemporal, optogenetic control of gene expression in organoids
Creators Name:Legnini, I. and Emmenegger, L. and Zappulo, A. and Rybak-Wolf, A. and Wurmus, R. and Oliveras Martinez, A. and Cerda Jara, C. and Boltengagen, A. and Hessler, T. and Mastrobuoni, G. and Kempa, S. and Zinzen, R. and Woehler, A. and Rajewsky, N.
Abstract:Organoids derived from stem cells have become an increasingly important tool for studying human development and modeling disease. However, methods are still needed to control and study spatiotemporal patterns of gene expression in organoids. Here we combined optogenetics and gene perturbation technologies to activate or knock-down RNA of target genes in programmable spatiotemporal patterns. To illustrate the usefulness of our approach, we locally activated Sonic Hedgehog (SHH) signaling in an organoid model for human neurodevelopment. Spatial and single-cell transcriptomic analyses showed that this local induction was sufficient to generate stereotypically patterned organoids and revealed new insights into SHH’s contribution to gene regulation in neurodevelopment. With this study, we propose optogenetic perturbations in combination with spatial transcriptomics as a powerful technology to reprogram and study cell fates and tissue patterning in organoids.
Keywords:Cell Differentiation, Gene Expression, Hedgehog Proteins, Optogenetics, Organoids, Substances
Source:Nature Methods
ISSN:1548-7091
Publisher:Nature Publishing Group
Volume:20
Number:10
Page Range:1544-1552
Date:October 2023
Official Publication:https://doi.org/10.1038/s41592-023-01986-w
PubMed:View item in PubMed

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