Cell-type-specific mRNA transcription and degradation kinetics in zebrafish embryogenesis from metabolically labeled single-cell RNA-seq

Lior Fishman, Avani Modak, Gal Nechooshtan, Talya Razin, Florian Erhard, Aviv Regev, Jeffrey A. Farrell () and Michal Rabani ()
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Lior Fishman: The Hebrew University of Jerusalem
Avani Modak: NIH
Gal Nechooshtan: The Hebrew University of Jerusalem
Talya Razin: The Hebrew University of Jerusalem
Florian Erhard: Institute for Virology and Immunobiology, University of Würzburg
Aviv Regev: MIT
Jeffrey A. Farrell: NIH
Michal Rabani: The Hebrew University of Jerusalem

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract During embryonic development, pluripotent cells assume specialized identities by adopting particular gene expression profiles. However, systematically dissecting the relative contributions of mRNA transcription and degradation to shaping those profiles remains challenging, especially within embryos with diverse cellular identities. Here, we combine single-cell RNA-Seq and metabolic labeling to capture temporal cellular transcriptomes of zebrafish embryos where newly-transcribed (zygotic) and pre-existing (maternal) mRNA can be distinguished. We introduce kinetic models to quantify mRNA transcription and degradation rates within individual cell types during their specification. These models reveal highly varied regulatory rates across thousands of genes, coordinated transcription and destruction rates for many transcripts, and link differences in degradation to specific sequence elements. They also identify cell-type-specific differences in degradation, namely selective retention of maternal transcripts within primordial germ cells and enveloping layer cells, two of the earliest specified cell types. Our study provides a quantitative approach to study mRNA regulation during a dynamic spatio-temporal response.

Date: 2024
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DOI: 10.1038/s41467-024-47290-9

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