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Spatio-temporal, optogenetic control of gene expression in organoids

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Title:Spatio-temporal, optogenetic control of gene expression in organoids
Creators Name:Legnini, I. and Emmenegger, L. and Zappulo, A. and Wurmus, R. and Oliveras Martinez, A. and Cerda Jara, C. and Boltengagen, A. and Hessler, T. and Mastrobuoni, G. and Rybak-Wolf, A. and Kempa, S. and Zinzen, R.P. and Woehler, A. and Rajewsky, N.
Abstract:Organoids derived from stem cells become increasingly important to study human development and to model disease. However, methods are needed to control and study spatio-temporal patterns of gene expression in organoids. To this aim, we combined optogenetics and gene perturbation technologies to activate or knock-down RNA of target genes, at single-cell resolution and in programmable spatio-temporal patterns. To illustrate the usefulness of our approach, we locally activated Sonic Hedgehog (SHH) signaling in an organoid model for human neurodevelopment. High-resolution spatial transcriptomic and single-cell analyses showed that this local induction was sufficient to generate stereotypically patterned organoids in three dimensions 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:Organoids, Optogenetics, Spatial Transcriptomics, Single-Cell Transcriptomics, CRISPR/Cas, Neurodevelopment, Sonic Hedgehog (SHH)
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2021.09.26.461850v3
Date:9 February 2022
Official Publication:https://doi.org/10.1101/2021.09.26.461850

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