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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.27.609971
preprint
1
Article
Dissecting the regulatory logic of specification and differentiation during vertebrate embryogenesis
Liu Jialin
Castillo-Hair Sebastian M.
Du Lucia Y.
Wang Yiqun
Carte Adam N.
Colomer-Rosell Mariona
Yin Christopher
Seelig Georg
Schier Alexander F.
27 8 2024
2024.08.27.609971https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.27.609971
nihpp-2024.08.27.609971.pdf
The interplay between transcription factors and chromatin accessibility regulates cell type diversification during vertebrate embryogenesis. To systematically decipher the gene regulatory logic guiding this process, we generated a single-cell multi-omics atlas of RNA expression and chromatin accessibility during early zebrafish embryogenesis. We developed a deep learning model to predict chromatin accessibility based on DNA sequence and found that a small number of transcription factors underlie cell-type-specific chromatin landscapes. While Nanog is well-established in promoting pluripotency, we discovered a new function in priming the enhancer accessibility of mesendodermal genes. In addition to the classical stepwise mode of differentiation, we describe instant differentiation, where pluripotent cells skip intermediate fate transitions and terminally differentiate. Reconstruction of gene regulatory interactions reveals that this process is driven by a shallow network in which maternally deposited regulators activate a small set of transcription factors that co-regulate hundreds of differentiation genes. Notably, misexpression of these transcription factors in pluripotent cells is sufficient to ectopically activate their targets. This study provides a rich resource for analyzing embryonic gene regulation and reveals the regulatory logic of instant differentiation.
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