TEMPO enables sequential genetic labeling and manipulation of vertebrate cell lineages

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• dc.contributor.author Espinosa-Medina, Isabel
• dc.contributor.author Feliciano, Daniel
• dc.contributor.author Belmonte Mateos, Carla, 1992-
• dc.contributor.author Miyares, Rosa Linda
• dc.contributor.author Garcia-Marques, Jorge
• dc.contributor.author Foster, Benjamin
• dc.contributor.author Lindo, Sarah
• dc.contributor.author Pujades Corbi, Cristina
• dc.contributor.author Koyama, Minoru
• dc.contributor.author Lee, Tzumin
• dc.date.accessioned 2023-03-14T07:14:57Z
• dc.date.available 2023-03-14T07:14:57Z
• dc.date.issued 2023
• dc.description.abstract During development, regulatory factors appear in a precise order to determine cell fates over time. Consequently, to investigate complex tissue development, it is necessary to visualize and manipulate cell lineages with temporal control. Current strategies for tracing vertebrate cell lineages lack genetic access to sequentially produced cells. Here, we present TEMPO (Temporal Encoding and Manipulation in a Predefined Order), an imaging-readable genetic tool allowing differential labeling and manipulation of consecutive cell generations in vertebrates. TEMPO is based on CRISPR and powered by a cascade of gRNAs that drive orderly activation and inactivation of reporters and/or effectors. Using TEMPO to visualize zebrafish and mouse neurogenesis, we recapitulated birth-order-dependent neuronal fates. Temporally manipulating cell-cycle regulators in mouse cortex progenitors altered the proportion and distribution of neurons and glia, revealing the effects of temporal gene perturbation on serial cell fates. Thus, TEMPO enables sequential manipulation of molecular factors, crucial to study cell-type specification.
• dc.format.mimetype application/pdf
• dc.identifier.citation Espinosa-Medina I, Feliciano D, Belmonte-Mateos C, Linda Miyares R, Garcia-Marques J, Foster B, Lindo S, Pujades C, Koyama M, Lee T. TEMPO enables sequential genetic labeling and manipulation of vertebrate cell lineages. Neuron. 2023 Feb 1;111(3):345-61.e10. DOI: 10.1016/j.neuron.2022.10.035
• dc.identifier.doi http://dx.doi.org/10.1016/j.neuron.2022.10.035
• dc.identifier.issn 0896-6273
• dc.identifier.uri http://hdl.handle.net/10230/56215
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Neuron. 2023 Feb 1;111(3):345-61.e10
• dc.rights © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword CRISPR
• dc.subject.keyword Cell cycle
• dc.subject.keyword Cell fate
• dc.subject.keyword Cell lineage
• dc.subject.keyword Gliogenesis
• dc.subject.keyword Mouse cortex
• dc.subject.keyword Neurogenesis
• dc.subject.keyword Zebrafish hindbrain
• dc.title TEMPO enables sequential genetic labeling and manipulation of vertebrate cell lineages
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion