Barcoding Notch signaling in the developing brain.

Autor:	Siniscalco AM; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Perera RP; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Greenslade JE; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Veeravenkatasubramanian H; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Masters A; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Doll HM; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Raj B; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.; Institute for Regenerative Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2024 Nov 22. Date of Electronic Publication: 2024 Nov 22.
DOI:	10.1242/dev.203102
Abstrakt:	Developmental signaling inputs are fundamental for shaping cell fates and behavior. However, traditional fluorescent-based signaling reporters have limitations in scalability and molecular resolution of cell types. We present SABER-seq, a CRISPR-Cas molecular recorder that stores transient developmental signaling cues as permanent mutations in cellular genomes for deconstruction at later stages via single-cell transcriptomics. We applied SABER-seq to record Notch signaling in developing zebrafish brains. SABER-seq has two components: a signaling sensor and a barcode recorder. The sensor activates Cas9 in a Notch-dependent manner with inducible control while the recorder obtains mutations in ancestral cells where Notch is active. We combine SABER-seq with an expanded juvenile brain atlas to identify cell types derived from Notch-active founders. Our data reveals rare examples where differential Notch activities in ancestral progenitors are detected in terminally differentiated neuronal subtypes. SABER-seq is a novel platform for rapid, scalable and high-resolution mapping of signaling activity during development. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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