Spatiotemporal, optogenetic control of gene expression in organoids.
Journal
Nature methods
ISSN: 1548-7105
Titre abrégé: Nat Methods
Pays: United States
ID NLM: 101215604
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
21
04
2023
accepted:
25
07
2023
medline:
26
10
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37735569
doi: 10.1038/s41592-023-01986-w
pii: 10.1038/s41592-023-01986-w
pmc: PMC10555836
doi:
Substances chimiques
Hedgehog Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1544-1552Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : RA838/5-1
Organisme : European Molecular Biology Organization (EMBO)
ID : ALTF1235-206
Informations de copyright
© 2023. The Author(s).
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